bluuebunny/crossref_metadata_2025 huggingface dataset:
The Three-Legged Stool: Synthesizing and Extending Our Understanding of the Career Advancement Facilitators of Persons With Disabilities in Leadership Positions
Authors: Samosh Daniel
Published: February 2020

I examine the career advancement facilitators of organizational stakeholders who may be identified as simultaneously “core” and “fringe” in this article, via the insights of 21 leaders with disabilities. To navigate barriers and advance their careers, these leaders benefited from three categories of facilitators, including career self-management strategies, social networks, and organizational and societal factors. Facilitators are synthesized with a metaphor, the three-legged stool, which depicts three foundational pillars that underlie the leaders’ success. Focusing on an understudied element of the social networks pillar, I examine how leaders’ external networks (family, friends, acquaintances, and role models) facilitated their career advancement. Findings point to the role of strong and weak ties in developing leaders’ career self-management strategies as well as their access to core stakeholder positions. Last, contributions, implications, and limitations of this article are discussed.
Valuing Value in Innovation Ecosystems: How Cross-Sector Actors Overcome Tensions in Collaborative Sustainable Business Model Development
Authors: Oskam Inge , Bossink Bart , de Man Ard-Pieter
Published: February 2020

This article aims to uncover the processes of developing sustainable business models in innovation ecosystems. Innovation ecosystems with sustainability goals often consist of cross-sector partners and need to manage three tensions: the tension of value creation versus value capture, the tension of mutual value versus individual value, and the tension of gaining value versus losing value. The fact that these tensions affect all actors differently makes the process of developing a sustainable business model challenging. Based on a study of four sustainably innovative cross-sector collaborations, we propose that innovation ecosystems that develop a sustainable business model engage in a process of valuing value in which they search for a result that satisfies all actors. We find two different patterns of valuing value: collective orchestration and continuous search. We describe these patterns and the conditions that give rise to them. The identification of the two patterns opens up a research agenda that can shed further light on the conditions that need to be in place in order for an innovation ecosystem to develop effective sustainable business models. For practice, our findings show how cross-sector actors in innovation ecosystems may collaborate when developing a business model around emerging sustainability-oriented innovations.
Countries and Cultural Differences in the Stigma of Mental Illness: The East–West Divide
Authors: Krendl Anne C. , Pescosolido Bernice A.
Published: February 2020

Mental illness is a global public health crisis. Although rates of untreated cases stand as a primary problem, stigma is a significant obstacle. Yet, global differences in levels and roots of stigma remain poorly understood. Using the Stigma in Global Context–Mental Health Study (SGC-MHS) data, we analyzed data on two components of stigma—prejudice and discriminatory potential—attached to clinically diagnostic cases of depression and schizophrenia. We examined whether stigma was higher in the East than West. Furthermore, we hypothesized that the link between prejudice and discriminatory potential in the East was due, in part, to cultural differences in the attributions about mental illness. With SGC-MHS’ nationally representative vignette data from over 11,000 respondents in 11 relevant countries (four Eastern, seven Western), analyses replicated past research of higher levels of stigma and more moral attributions in Eastern countries, particularly for depression. Moreover, prejudice-related disclosure spillover concerns predicted discriminatory potential (social distance) in the East, but not the West; this was driven by a greater emphasis on moral attributions in the East. Finally, exploratory analyses found that Western respondents endorsed higher discrimination for minority (vs. majority) group members with mental illness. In Eastern countries, the same pattern emerged for schizophrenia, but the reverse occurred for depression—greater stigma for majority as compared with minority group members. Together, these findings suggest that cultural differences in the sources of prejudice and attributions about the etiology of mental illness contribute, at least in part, to global differences in the profile of stigma.
The influence of collectivistic personal values on the formation of entrepreneurial intentions
Authors: Hueso Juan Alberto , Jaén Inmaculada , Liñán Francisco , Basuki Whysnianti
Published: February 2020

This article analyses the specific role of collectivistic personal values as an antecedent of entrepreneurial intention. While previous studies have focused on individualistic values, the influence of collectivistic values has remained largely ignored. We study this influence on a sample of 413 university students from the United Kingdom and Spain. The results are consistent in both countries, suggesting that an emphasis on collectivistic personal values triggers an indirect, negative effect on entrepreneurial intentions through both personal attitude and perceived behavioural control. However, it also induces an indirect positive effect through subjective norms. The study indicates that not only individualistic values but the complete personal-value structure is influential in explaining the formation of entrepreneurial intentions.
Use of pulmonoplegia and delivery system during recipient surgery in lung transplantation
Authors: Shade Brandon C , Dudley Steven , McCabe Tara , Gray-DeAngelis Kathryn
Published: February 2020

Lung transplantation in the United States has steadily grown over the last decade. Major attention has been with the understanding of lung ischemia–reperfusion injury and how it relates to primary graft dysfunction. In 2015, our institution implemented the use of a pulmonoplegia solution during recipient surgery of lung transplantation. A unique circuit utilizing the heart lung machine is used to deliver the pulmonoplegia solution. This system is considered to be a key contributing factor to the success of our lung transplant program.
Natural Canine Distemper Virus Infection in Linnaeus’s 2-Toed Sloths (Choloepus didactylus)
Authors: Watson Allison M. , Cushing Andrew C. , Sheldon Julie D. , Anis Eman , Wilkes Rebecca P. , Dubovi Edward J. , Craig Linden E.
Published: February 2020

An outbreak of canine distemper virus in a private zoo in eastern Tennessee in July 2016 led to fatal clinical disease in 5 adult, wild-caught Linnaeus’s 2-toed sloths ( Choloepus didactylus). Clinical signs included hyporexia, lethargy, mucopurulent nasal discharge, and oral and facial ulcers. At necropsy, affected animals had crusts and ulcers on the lips, nose, tongue, and oral cavity. Microscopically, all sloths had widespread, random, hepatic necrosis; lymphoid depletion; and bronchointerstitial pneumonia. The central nervous system did not contain gross or histopathologic lesions in any of the 5 sloths, although immunoreactivity for viral antigen was present within vessel walls. Epithelial cells and histiocytes within numerous organs contained intranuclear and intracytoplasmic inclusions and occasional syncytial cells. Canine distemper virus was confirmed with immunohistochemistry and virus isolation. Viral sequencing identified the novel American-4 strain prevalent in eastern Tennessee wildlife. This is the first pathologic characterization of canine distemper virus infection in sloths (family Choloepodidae, order Pilosa) and emphasizes the significant morbidity and mortality in this species.
Generation and Validation of an Antibody to Canine CD19 for Diagnostic and Future Therapeutic Purposes
Authors: Haran Kumudhini Preethi , Lockhart Alexandra , Xiong Ailian , Radaelli Enrico , Savickas Patrick J. , Posey Avery , Mason Nicola J.
Published: February 2020

The B-cell coreceptor, CD19 is a transmembrane protein expressed throughout B-cell ontogeny from pro–B cell to plasmablast. It plays an important role in B-cell development and function and is an attractive target for antibody-directed immunotherapies against B-cell malignancies, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (B-NHL) in humans. With the rapid development of next-generation immunotherapies aimed at improving therapeutic efficacy, there is a pressing need for a clinically relevant, immune-competent, spontaneous animal model to derisk these new approaches and inform human immunotherapy clinical trials. Pet dogs develop spontaneous B-cell malignancies, including B-NHL and leukemias that share comparable oncogenic pathways and similar immunosuppressive features to human B-cell malignancies. Despite treatment with multiagent chemotherapy, durable remissions in canine B-NHL are rare and most dogs succumb to their disease within 1 year of diagnosis. Here we report the development and validation of an anti-canine CD19-targeting monoclonal antibody and its single-chain derivatives, which enable next-generation CD19-targeted immunotherapies to be developed and evaluated in client-owned dogs with spontaneous B-NHL. These future in vivo studies aim to provide important information regarding the safety and therapeutic efficacy of CD19-targeted mono- and combination therapies and identify correlative biomarkers of response that will help to inform human clinical trial design. In addition, development of canine CD19-targeted immunotherapies aims to provide better therapeutic options for pet dogs diagnosed with B-cell malignancies.
A Novel Neorickettsial Infection in 3 Dogs in the Pacific Northwest
Authors: Pastenkos Gabrielle , Snekvik Kevin , Bradway Dan , Cerchiaro Ilaria , Mehain Susan , Krytenberg Denise , Eckstrand Chrissy
Published: February 2020

The genus Neorickettsia includes obligate, intracellular bacteria responsible for diseases including Potomac horse fever caused by Neorickettsia risticii and salmon poisoning disease (SPD) caused by Neorickettsia helminthoeca. The Stellanchasmus falcatus (SF) agent is a member of this genus previously associated only with mild clinical signs in dogs. Between 2013 and 2016, 3 dogs in Washington State (USA) presented with disease suggestive of SPD, but N. helminthoeca was not detected by molecular techniques. Clinical signs included depression, anorexia, and diarrhea. Cytologic examination of aspirates supported a diagnosis of granulomatous lymphadenitis with organisms suggestive of Neorickettsia. Dogs either died or were humanely euthanized due to poor response to therapy. Necropsy findings included lymphadenomegaly and hepatomegaly. Histopathology identified granulomatous and lymphoplasmacytic splenitis, lymphadenitis, enteritis, and hepatitis with extensive necrosis. Neorickettsia DNA was detected using genus-specific primers and direct sequencing showed 100% sequence identity to the SF agent in all 3 dogs. This is the first clinicopathologic description of severe disease in dogs attributed to the SF agent. These findings may suggest the emergence of a novel neorickettsial disease in the Pacific Northwest.
Dynamic and Stochastic Shipment Matching Problem in Multimodal Transportation
Authors: Guo Wenjing , Atasoy Bilge , Beelaerts van Blokland Wouter , Negenborn Rudy R.
Published: February 2020

Multimodal transportation, as an efficient and sustainable alternative to unimodal transportation, refers to the utilization of multiple modes, the utilization of standard loading units, and flexibility in planning. The complexity of multimodal transportation at the operational level lies in being able to deal with dynamic events that are unknown before their realization. However, stochastic information on some of the events might be available from historical data. This paper proposes an anticipatory optimization approach to handle dynamic shipment requests in multimodal transportation by incorporating stochastic information of requests’ origin, destination, volume, announce time, release time and due time. The experimental results show that the anticipatory approach outperforms a myopic approach in which decisions are made only based on deterministic information in reducing total costs under various scenarios of the multimodal matching system.
Precise tip-positioning control of a single-link flexible arm using a fractional-order sliding mode controller
Authors: Hamzeh Nejad Farzaneh , Fayazi Ali , Ghayoumi Zadeh Hossein , Fatehi Marj Hassan , HosseinNia S Hassan
Published: February 2020

This article presents an efficient scheme based on fractional order sliding mode control approach for precision tip position control of a single link flexible robot arm. The proposed control strategy is robust against the system parameters variations such as payload and viscous friction variations in the presence of the sinusoidal disturbance and the unknown Coulomb friction disturbances. The aim of controller design is reduction of the deviation caused by the link flexibility and then the precision tip positioning control of the single-link flexible arm. In this regard, sliding mode control strategy is performed in two stages. In the first stage, the difference between the motor angle (load angle) and the tip angle of the flexible link is reduced by applying the proposed fractional order sliding mode controller and then, in the second step, the precision tracking of the tip position of the link is done by adding another sliding mode control scheme. The feasibility and effectiveness of the proposed control scheme is demonstrated via numerical simulation results.
The right methodology for long-term vascular access research: Three burning questions
Authors: Balsorano Paolo , Pinelli Fulvio
Published: February 2020

Over the last 20 years, there has been a great proliferation of studies of different aspects of the long-term vascular access field. Despite the availability of such studies, methodological pitfalls surrounding long-term vascular access research are rarely mentioned. Methodological issues inherent to retrospective analyses make them very poor tools for providing generalizable results, as they often become estimates of local experiences rather than reflections of up-to-date practices. Second, despite being an often-ignored element when designing studies on catheter-related complications, a proper follow-up time definition and its length are crucial to limiting the impact of attrition bias on research results. Finally, meta-analyses constitute a powerful tool in modern evidence-based era, but several pitfalls can affect overall results. When designing a systematic review and meta-analytic process, study selection should always reflect the relevance of clinical questions and the capability to contextualize results in the modern and evidence-based vascular access era.
Factors influencing outcomes of rheolytic thrombectomy on thrombosed dialysis access grafts: Door to angiographic bed time and what else?
Authors: Ierardi Anna Maria , Carnevale Aldo , Coppola Andrea , Renzulli Matteo , Crippa Matteo , Fumarola Enrico Maria , Golfieri Rita , Giganti Melchiore , Carrafiello Gianpaolo
Published: February 2020

Background:

The aim of this study was to investigate the effect of the time interval from clinical presentation of arteriovenous graft thrombosis and the thrombectomy procedure by the AngioJet system in terms of technical and clinical success and to identify factors influencing success.

Methods:

A total of 60 consecutive patients (35 men and 25 women; mean age = 52 ± 7.89 years) who had undergone percutaneous thrombectomy by the AngioJet device from 2016 to 2019 were retrospectively enrolled. Demographics and fistula data, previous treatments, time from clinical onset of thrombosis to intervention, procedural details and complications were recorded. Technical and clinical success and primary and secondary patency rates were calculated. One-way analysis of variance was performed to test any correlation between patient-related and fistula/procedure-related variables and technical/clinical success. Odds ratio and relative risk were also calculated when necessary.

Results:

Technical success and clinical success were 95% and 91.7%, respectively. Post-interventional primary and secondary patency rates at 1 year were 72.5% and 84.3%, respectively. Complication rate was 6.7%. One-way analysis of variance showed that clinical success was higher in patients with no previous treatment (p = 0.015). Furthermore, clinical success was significantly associated with door to angiographic bed time (p = 0.002): p-value for the 24-h and the 72-h cut-off was 0.012 and 0.006, respectively.

Conclusion:

Percutaneous rheolytic thrombectomy is safe and effective for thrombosed arteriovenous grafts, with acceptable primary and secondary patency rates. Higher clinical success was found in patients never treated before and when the procedure was carried out within 24 h from the clinical onset of thrombosis.
Delivering developmentally appropriate health care: Roles for psychologists as members of the multi-disciplinary health care team
Authors: Dovey-Pearce Gail , Rapley Tim , McDonagh Janet E
Published: February 2020

There is increasing global attention on the health and wellbeing needs of young people. Preventive and proactive approaches will likely lead to the clearest dividends for young people, their own children and wider society. A brief overview of the international context for young people’s health care is given. As well as influencing policy, there are important roles for the health care team, including psychologists, to influence the organisations they work within, advocating for the needs of young people and their families. This is the focus of this article. The concept of developmentally appropriate health care (DAH) for young people is explored. It could help when planning services and approaches that respond to the needs of young people. Building relationships is likely to be key, to connect with young people to help them make health and wellbeing decisions, and provide individualised support. The ‘connectedness’ research could also be helpful in looking beyond the health care evidence. A key challenge for psychologists and their multi-disciplinary health care colleagues, in practice and research, is to move away from a reliance on binary, easier-to-measure health and wellbeing outcomes and, instead, find ways to promote and measure developmental outcomes that are meaningful to young people and their families.
An intelligent real-time scheduler for out-patient clinics: A multi-agent system model
Authors: Munavalli Jyoti R , Rao Shyam Vasudeva , Srinivasan Aravind , van Merode GG
Published: February 2020

Scheduling of resources and patients are crucial in outpatient clinics, particularly when the patient demand is high and patient arrivals are random. Generally, outpatient clinic systems are push systems where scheduling is based on average demand prediction and is considered for long term (monthly or bimonthly). Often, planning and actual scenario vary due to uncertainty and variability in demand and this mismatch results in prolonged waiting times and under-utilization of resources. In this article, we model an outpatient clinics as a multi-agent system and propose an intelligent real-time scheduler that schedules patients and resources based on the actual status of departments. Two algorithms are implemented: one for resource scheduling that is based on predictive demand and the other is patient scheduling which performs path optimization depending on the actual status of departments. In order to match resources with stochastic demand, a coordination mechanism is developed that reschedules the resources in the outpatient clinics in real time through auction-bidding procedures. First, a simulation study of intelligent real-time scheduler is carried out followed by implementation of the same in an outpatient clinic of Aravind Eye Hospital, Madurai, India. This hospital has huge patient demand and the patient arrivals are random. The results show that the intelligent real-time scheduler improved the performance measures like waiting time, cycle time, and utilization significantly compared to scheduling of resources and patients in isolation. By scheduling resources and patients, based on system status and demand, the outpatient clinic system becomes a pull system. This scheduler transforms outpatient clinics from open loop system to closed-loop system.
Electoral system influence on social network usage patterns of parliamentary assistants as their legislators’ stand-in: The United States, Germany, and Israel
Authors: Sabag Ben-Porat Chen , Lehman-Wilzig Sam
Published: February 2020

Social networks are generally regarded as channels through which parliamentarians establish direct contact with the public. However, do they engage in these activities personally or rather delegate them to their parliamentary assistants? This study examines the intermediary relationship between parliamentarians and the public (henceforth PAs)—seeking to understand their role in contemporary, political communications. While numerous studies have looked at types of parliamentarian contact with the public, PAs have received little scholarly attention. Adopting a comparative perspective, this study will suggest a theoretical model of the MP/PA social media work relationship, creating a new questionnaire for PAs in the US House of Representatives, German Bundestag, and Israeli Knesset, exploring whether level of parliamentarians’ involvement in social networking is influenced by working within different electoral systems: representatives elected directly (the United States), mixed (Germany), and indirectly (Israel). The study investigates the level of parliamentarians’ engagement with social media communication according to a four-category model.
Parenting in the digital age: Between socio-biological and socio-technological development
Authors: Jeffery Catherine Page
Published: February 2020

Parents have long been encouraged to treat their child’s development as a capability, with the imperative being to maximize this capability. At the same time, however, children’s ‘natural’ process of development must be allowed to take its course. Digital media technologies promise to not only enhance children’s developmental capacity, but also threaten to disrupt their normal development. Drawing on qualitative research involving 40 Australian parents, this article examines parents’ concerns about their teenage children’s use of digital media. It examines how parents negotiate the tension between technological development and the benefits it affords their child, and the perceived risks that technological development poses to their child’s normal development, through mediating what they construct as positive and negative exposure to digital media. Parents distinguished between media use that was considered to enhance their child’s development and use that had the potential to disrupt it, by categorizing various activities as appropriate and inappropriate.
Stories as findings in collaborative research: making meaning through fictional writing with disadvantaged young people
Authors: Satchwell Candice , Larkins Cath , Davidge Gail , Carter Bernie
Published: February 2020

Working in a participatory research project with young people who are disabled, care-experienced or otherwise disadvantaged, collaborative fiction writing was a core method of hearing and amplifying their voices. We discuss how meanings were made in this iterative process of capturing resonances in the different stages of the research, resulting in the creation of stories filtered through many different participants. Through individual and joint reflections on the complex processes of constructing the 48 short stories, we demonstrate how collective storytelling can address criticisms of fictional research outputs as (in)valid social science, and argue instead that the resulting stories can be considered rigorous and faithful research findings. We suggest that these research outputs preserve and proliferate the meanings of marginalised young people, and challenge the absence or distortion of existing narratives about their lives as experienced by themselves.
Parent Attendance in a Family-Based Preventive Intervention Delivered in Latin America and the United States
Authors: Rojas Lourdes M. , Ochoa Lucas G. , Sánchez Ahumada Marcelo , Quevedo Ana , Muñoz Viviana , Condo Cecilia , Prado Guillermo
Published: February 2020

In Latin America, there is an increasing interest in the implementation and dissemination of evidence-based, family-centered interventions to prevent youth behavioral problems. While families’ participation in interventions is integral to achieving the interventions’ desired impact, little is known about what predicts Latin American families’ attendance. The current study provides a unique opportunity to explore the participation of families living in the United States, Ecuador, and Chile in an evidence-based intervention, Familias Unidas. We tested for differences in attendance rates, family functioning variables, and adolescent behavioral problem variables, then applied a hierarchical multiple regression to (a) identify which variables significantly predicted program attendance and (b) assess whether the country in which the intervention was implemented in moderated the relationship between predictors and program attendance. On average, Chilean and Ecuadorian parents were more engaged and attended more sessions than parents living in the United States. Across samples, there was significant differences in family functioning and adolescent behavioral problem variables. However, effective parent–adolescent communication was the only significant predictor of lower program attendance. A significant interaction effect revealed that even though Chilean parents had high parent–adolescent communication, they were more likely to attend sessions, compared to parents living in the United States. We highlight the promise of engaging and retaining families, across U.S. and Latin American samples, into a culturally syntonic, family-based intervention, and discuss potential explanations for success in Chile and Ecuador. Researchers interested in implementing interventions in Latin America could utilize these findings to better target participants and intervention efforts.
Redesigning College Professional Development Resources to Meet the Needs of Emerging Public Health Professionals
Authors: Torrens Armstrong Anna , Corvin Jaime A. , Azeredo Juliana , Burke Somer , Carr Caitlynn C. , King Christopher
Published: February 2020

The University of South Florida, College of Public Health, is dedicated to providing career planning and professional development services for students in varying formats. However, changing public health training needs and an emerging need for focused attention on professional development necessitated the development of an evaluative program to better understand our students’ needs in these areas. Specifically, anecdotal student feedback about feeling unprepared professionally and survey feedback from students, preceptor feedback regarding the need for students to be better trained in core professional concepts, and low rates of attendance in standard professional development events resulted in a quality improvement study to identify students’ perceived career planning and professional development needs. Findings were used to redesign current services and provided the basis for developing more targeted trainings to ensure that public health graduates are better prepared to meet employer expectations and to excel in the workforce. This article provides an overview of this transformative process, including the results of the qualitative survey on student, faculty, alumni, and community preceptor perspectives, and resulting prototypes developed for the professional development pilot along with preliminary insights.
From the Editors
Authors: Ray Rashawn , Rojas Fabio
Published: February 2020

Contexts editors Rashawn Ray and Fabio Rojas introduce a special issue on some of the experiences of a diverse range of workers.
The Social Psychology Behind Teacher Walkouts
Authors: Everitt Judson
Published: February 2020

Why are we seeing so many teacher walkouts when traditional collective bargaining for teachers has weakened considerably in recent decades? A key part of the answer involves the social psychology through which teachers develop their professional culture, and how the evolution of accountability has been toxic to that culture.
Polluted Bodies
Authors: Masi de Casanova Erynn
Published: February 2020

Domestic employment requires unique physical proximity of bodies from different social classes, and often from different racial and ethnic backgrounds. Despite the physical closeness, different strategies are used to reproduce class hierarchies among people, resulting in embodied inequality.
Of Love and Exploitation
Authors: Vázquez Karina Elizabeth
Published: February 2020

By speaking through Cleo, Cuarón offers the working elite a narrative to ease their own anxieties around class instability.
Thriving as a Sociology Graduate
Authors: Senter Mary Scheuer , Spalter-Roth Roberta
Published: February 2020

Students major in sociology because they want to understand social life and social change, but does wanting a meaningful career equal a large salary? As it turns out, while sociology graduates do not earn top dollars in their first year out of undergraduate school, their salaries do increase and usually double by ten years out.
Reenvisioning Pay for Play
Authors: Brown Kevin , Williams Antonio
Published: February 2020

California recently passed the Fair Pay to Play Act, allowing college athletes to be paid for endorsements, making income off of their likeness. While many people are heralding this bill, we propose that sports revenue could be used to decrease the racial education gap in the local communities that are often preyed upon by elite sports programs.
Culture of Fear and the Presidential Scare
Authors: Glassner Barry
Published: February 2020

In the current edition of the book, The Culture of Fear, many of the new chapters to the Fearmonger-in-Chief, Donald Trump.
CryptoKitties and the New Ludic Economy: How Blockchain Introduces Value, Ownership, and Scarcity in Digital Gaming
Authors: Serada Alesja , Sihvonen Tanja , Harviainen J. Tuomas
Published: February 2020

This article analyzes specific characteristics of value created through digital scarcity and blockchain-proven ownership in cryptogames. Our object of study is CryptoKitties, the first instance of a blockchain-based game that has garnered media recognition and financial interest. The objective of this article is to demonstrate the limits of scarcity in value construction for owners of CryptoKitties tokens, manifested as breedable virtual cats. Our work extends the trends set out by earlier cryptocurrency studies from the perspective of cultural studies. For the purpose of this article, we rely on open blockchain analytics such as DappRadar and Etherscan, as well as player-created analytics, backed by a one-year-long participant observation period in the said game for research material. Combining theoretical cryptocurrency and Bitcoin studies, open data analysis, and virtual ethnography enables a grounded discussion on blockchain-based game design and play.
Correlating imaging parameters with molecular data: An integrated approach to improve the management of breast cancer patients
Authors: Incoronato Mariarosaria , Mirabelli Peppino , Grimaldi Anna Maria , Soricelli Andrea , Salvatore Marco
Published: February 2020

The goal of this review is to provide an overview of the studies aimed at integrating imaging parameters with molecular biomarkers for improving breast cancer patient’s diagnosis and prognosis. The use of diagnostic imaging to extract quantitative parameters related to the morphology, metabolism, and functionality of tumors, as well as their correlation with cancer tissue biomarkers is an emerging research topic. Thanks to the development of imaging biobanks and the technological tools required for extraction of imaging parameters including radiomic features, it is possible to integrate imaging markers with genetic data. This new field of study represents the evolution of radiology–pathology correlation from an anatomic–histologic level to a genetic level, which paves new interesting perspectives for breast cancer management.
Evolving use of liquid biopsy in non-small-cell-lung cancer patients
Authors: Indraccolo Stefano
Published: February 2020

Liquid biopsy is routinely used to detect epidermal growth factor receptor mutations in advanced or metastatic lung cancer, due to some limitations of tissue genotyping, especially at relapse. However, the existence of a non-marginal proportion of oncogene-addicted lung cancers that can benefit from target therapy is rapidly expanding clinical relevance of plasma genotyping. Apart from static assessment of mutations in circulating free DNA, the fact that liquid biopsy is minimally invasive and can be repeated several times makes it a suitable assay for the dynamic monitoring of cancer response to treatment. It is likely that quantitative mutation assessment by liquid biopsy will be increasingly included in the design of innovative clinical trials for patient stratification purposes.
A Critical Discourse of EI and CA in Emerging Economies: The Place of Nigeria Within the Global Innovation Ecosystems
Authors: Raimi Lukman , Yusuf Hassan
Published: February 2020

This study explores the levels of and barriers to entrepreneurial innovation (EI) and competitive advantage (CA) in emerging economies, and situates the findings within the Nigeria’s global innovation ecosystems. A qualitative research approach is preferred relying on the secondary data extracted from the reports of Global Competitiveness Index (GCI) and enriched by scholarly works including insights from the reports of Global Entrepreneurship Index (GEI). The extracted data from the afore-mentioned sources were critically reviewed and analysed using content analysis to understand the connection between EI and CA. At the end of the analysis, the study found that for 10 years (2008–2017), Nigeria manifested low EI and CA on the GCI ranking, whereas other African countries such as Ghana, Cameroon and South Africa, with lesser economic resources, did comparatively better. Second, it was found that, the key barriers to EI and CA are infrastructural neglect, lack of strong regulatory institutions, weak macroeconomic environment, weak technological readiness, poor business sophistication and low innovation among others. The study improves understanding of theoretical, managerial and policy implications of EI and CA. It also provides appropriate strategic suggestions for stimulating EI and enhancing CA at both national and industry levels in Nigeria. The study contributes to the raging debates on EI and CA in emerging economies. It also supports the Schumpeter’s creative discovery theory and resource-based view of CA.
Initiation of Emicizumab Therapy in an Adult Patient With Hemophilia A With Inhibitors and Associated Drug Cost Savings
Authors: Root Adam G. , Raiff Robert D. , Ortel Thomas L. , Hodulik Kimberly L.
Published: February 2020

Objective: To report the utilization of emicizumab in a patient with severe hemophilia A with inducible inhibitors and the reduction of drug costs related to decreased on-demand recombinant factor VIIa use. Case Summary: A 65-year-old African American man with established hemophilia A with an inducible factor VIII inhibitor presented with a bleeding hematoma from the right posterior thigh. The patient was historically managed on frequent administration of recombinant factor VIIa to achieve hemostasis and was started on every 2-hour dosing during this admission. Emicizumab, a new therapy for hemophilia A, became available during this admission, and the patient discontinued recombinant factor VIIa and transitioned to weekly emicizumab injections. The patient did not require any recombinant factor VIIa during the following 12 months resulting in substantial drug cost savings. Discussion: After initiation of emicizumab therapy, the patient no longer required on-demand treatment with recombinant factor VIIa for bleeds. Through this reduction in recombinant factor VIIa, there was a large decrease in inpatient drug costs and inpatient admissions for bleeding events. Conclusion: The potential reduction in drug costs and inpatient admissions should be considered when determining if emicizumab therapy is appropriate for hemophilia A patients with inhibitors. Further research is needed to confirm that continued long-term use of emicizumab remains associated with a reduction in on-demand treatment.
High level of fetal-globin reactivation by designed transcriptional activator-like effector
Authors: Zhan Jun , Irudayam Maria Johnson , Nakamura Yukio , Kurita Ryo , Nienhuis Arthur W.
Published: February 2020

The fetal-to-adult hemoglobin switch has been a focus of a long-standing effort to potentially treat sickle cell disease and β thalassemia by induction of fetal hemoglobin. In a continuation of this effort, we designed specific transcriptional activator-like effectors (TALEs) to target both the Gγ and Aγ-globin promoters. We fused the TALEs to a LIM domain binding protein (Ldb1) dimerization domain, followed by a T2A green fluorescent protein (GFP) cassette, which were assembled into a lentiviral vector. To prevent deletions caused by the repeats of TALEs during the lentivirus packing process, we changed the TALE encoding DNA by codon optimization. Intriguingly, 5 of 14 TALEs showed forced reactivation of fetal-globin expression in human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells, with a significant increase in the γ-globin mRNA level by more than 70-fold. We also observed a more than 50% reduction of β-globin mRNA. High-performance liquid chromatography analysis revealed more than 30% fetal globin in TALE-induced cells compared with the control of 2%. Among several promoters studied, the β-globin gene promoter with the locus control region (LCR) enhancer showed the highest TALE expression during CD34 erythroid differentiation. At day 19 of differentiation, 2 TALEs increased fetal-globin expression more than 40-fold in the mRNA level and up to 70% of the total globin protein. These TALEs have potential for clinical translation.
Correction to: Proteomic analysis of degradation ubiquitin signaling by ubiquitin occupancy changes responding to 26S proteasome inhibition
Authors: Hristova Ventzislava , Sun Shisheng , Zhang Hui , Chan Daniel W.
Published: February 2020

In the original publication of the article, Figure 2d was published incorrectly. The corrected Fig. 2 was given in this Correction article [1]. The original article has been corrected.
NucBreak: location of structural errors in a genome assembly by using paired-end Illumina reads
Authors: Khelik Ksenia , Sandve Geir Kjetil , Nederbragt Alexander Johan , Rognes Torbjørn
Published: February 2020

Background

Advances in whole genome sequencing strategies have provided the opportunity for genomic and comparative genomic analysis of a vast variety of organisms. The analysis results are highly dependent on the quality of the genome assemblies used. Assessment of the assembly accuracy may significantly increase the reliability of the analysis results and is therefore of great importance.

Results

Here, we present a new tool called NucBreak aimed at localizing structural errors in assemblies, including insertions, deletions, duplications, inversions, and different inter- and intra-chromosomal rearrangements. The approach taken by existing alternative tools is based on analysing reads that do not map properly to the assembly, for instance discordantly mapped reads, soft-clipped reads and singletons. NucBreak uses an entirely different and unique method to localise the errors. It is based on analysing the alignments of reads that are properly mapped to an assembly and exploit information about the alternative read alignments. It does not annotate detected errors. We have compared NucBreak with other existing assembly accuracy assessment tools, namely Pilon, REAPR, and FRCbam as well as with several structural variant detection tools, including BreakDancer, Lumpy, and Wham, by using both simulated and real datasets.

Conclusions

The benchmarking results have shown that NucBreak in general predicts assembly errors of different types and sizes with relatively high sensitivity and with lower false discovery rate than the other tools. Such a balance between sensitivity and false discovery rate makes NucBreak a good alternative to the existing assembly accuracy assessment tools and SV detection tools. NucBreak is freely available at https://github.com/uio-bmi/NucBreak under the MPL license.
Preterm birth impairs postnatal lung development in the neonatal rabbit model
Authors: Salaets Thomas , Aertgeerts Margo , Gie André , Vignero Janne , de Winter Derek , Regin Yannick , Jimenez Julio , Vande Velde Greetje , Allegaert Karel , Deprest Jan , Toelen Jaan
Published: February 2020

Background

Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits.

Methods

Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms.

Results

Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences.

Conclusions

Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.
Prevalence of HCV among people who inject drugs in Brussels—a respondent-driven sampling survey
Authors: Van Baelen Luk , Plettinckx Els , Antoine Jérôme , Gremeaux Lies
Published: February 2020

Background

In Belgium, people who inject drugs (PWID) are at a high risk of being infected by hepatitis C (HCV) as injecting drug use is the main mode for transmission of HCV in Europe. Estimates about the number of people living with HCV in Belgium are rare and even less is known about the prevalence of HCV among PWID.

Method

Between 1 February 2019 and 26 April 2019, PWID and high-risk opiate users (HROU) were recruited in Brussels through respondent-driven sampling (RDS). They were invited to a questionnaire and underwent a rapid HCV test.

Results

A total of 253 respondents participated in the study, of which 168 were PWID and 238 were HROU, with 153 respondents belonging to both categories. The overall unweighted sample average for HCV antibodies was 41.1%. The weighted population estimates were 43.7% (95% CI 30.6–56.8%) for RDS-II and 43.4% (95% CI 28.9–58.0%) for RDS-SS.

Conclusions

This prevalence is lower than the prevalence estimates reported elsewhere in Europe. However, the data still suggest that serious efforts are needed to reach the goal set by the WHO to reduce HCV by 2030 with 90%.
Atmiyata, a community-led intervention to address common mental disorders: Study protocol for a stepped wedge cluster randomized controlled trial in rural Gujarat, India
Authors: Joag Kaustubh , Kalha Jasmine , Pandit Deepa , Chatterjee Susmita , Krishnamoorthy Sadhvi , Shields-Zeeman Laura , Pathare Soumitra
Published: February 2020

Background

While lay-health worker models for mental health care have proven to be effective in controlled trials, there is limited evidence on the effectiveness and scalability of these models in rural communities in low- and middle-income countries (LMICs). Atmiyata is a rural community-led intervention using local community volunteers, called Champions, to identify and provide a package of community-based interventions for mental health, including evidence-based counseling for persons with common mental disorders (CMD).

Methods

The impact of the Atmiyata intervention is evaluated through a stepped wedge cluster randomized controlled trial (SW-CRCT) with a nested economic evaluation. The trial is implemented across 10 sub-blocks (645 villages) in Mehsana district in the state of Gujarat, with a catchment area of 1.52 million rural adults. There are 56 primary health centers (PHCs) in Mehsana district and villages covered under these PHCs are equally divided into four groups of clusters of 14 PHCs each. The intervention is rolled out in a staggered manner in these groups of villages at an interval of 5 months.

The primary outcome is symptomatic improvement measured through the GHQ-12 at a 3-month follow-up. Secondary outcomes include: quality of life using the EURO-QoL (EQ- 5D), symptom improvement measured by the Self-Reporting Questionnaire-20 (SRQ-20), functioning using the World Health Organization’s Disability Assessment Scale (WHO-DAS-12), depression symptoms using the Patient Health Questionnaire (PHQ-9), anxiety symptoms using Generalized Anxiety Disorder Questionnaire (GAD-7), and social participation using the Social Participation Scale (SPS). Generalized linear mixed effects model is employed for binary outcomes and linear mixed effects model for continuous outcomes. A Return on Investment (ROI) analysis of the intervention will be conducted to understand whether the intervention generates any return on financial investments made into the project.

Discussion

Stepped wedge designs are increasingly used a design to evaluate the real-life effectiveness of interventions. To the best of our knowledge, this is the first SW-CRCT in a low- and middle-income country evaluating the impact of the implementation of a community mental health intervention. The results of this study will contribute to the evidence on scaling-up lay health worker models for mental health interventions and contribute to the SW-CRCT literature in low- and middle-income countries.

Trial registration

The trial is registered prospectively with the Clinical Trial Registry in India and the Clinical Trial Registry number- CTRI/2017/03/008139. URL http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=70845.17209. Date of registration- 20/03/2017.