243 research outputs found

    Team perceived virtuality: an emergent state perspective

    Get PDF
    The rapid changes of work, the ease of mobility, and ubiquitous use of virtual tools have fundamentally changed the way that teamwork in modern organizations is accomplished. Although these developments have elicited a broad range of studies focusing on the phenomenon of team virtuality, the construct itself is still tied to conceptual ambiguities, opposing theoretical underpinnings, and inconsistent findings. The present paper synthesizes the structural and social-constructivist elements of team virtuality in order to introduce the novel concept of team perceived virtuality (TPV), embedded within a theoretical model of its team-level emergence. We define TPV as a cognitive-affective team emergent state which is grounded in collectively experienced feelings of distance and perceptions of information deficits. We further describe how TPV emerges as a function of team members’ collectively developed co-constructions and identify antecedents that contribute towards this emergence. By disentangling perceptions from structural properties, the present paper conceptually advances our understanding of team virtuality beyond its structural characteristics. Ultimately, this conceptual work serves as a starting point for future research on team virtuality as a collectively constructed, team-level emergent construct.info:eu-repo/semantics/acceptedVersio

    Identification and characterization of novel CD274 (PD‐L1) regulating microRNAs and their functional relevance in melanoma

    Full text link
    Background: Immune checkpoint inhibitors directed against programmed cell death 1 (PDCD1/PD1) receptor and programmed cell death-ligand 1 (CD274/PD-L1) have been recently successfully implemented for the treatment of many cancers, but the response rate of tumour patients is still limited due to intrinsic and acquired resistances. However, the underlying molecular mechanisms of this limited response have still to be defined in detail. The aim of this study is to uncover processes inhibiting PDCD1/CD274 expression thereby enhancing anti-tumour immune responses. The identification and characterization of microRNAs (miRNAs) targeting the 3′-untranslated region (3′-UTR) as well as the coding sequence (CDS) of CD274 will provide the basis for a new drug development. Methods: Human melanoma cell lines and tissue samples were subjected to mRNA and/or protein expression analysis using qPCR, Western blot, flow cytometry, and/or immunohistochemistry. The data were correlated to clinical parameters. MiRNA trapping by RNA in vitro affinity purification (miTRAP) technology in combination with small RNA sequencing and different bioinformatics tools were employed to identify CD274-regulating miRNAs. Results: Screening based on miTRAP in combination with RNAseq identified a large number of novel CD274-regulating candidate miRNAs, from which eight selected miRNAs were functionally validated. Five out of eight miRNAs were able to significantly reduce CD274 surface expression indicating that these miRNAs directly bind to the 3′-UTR or CDS of the CD274 gene. The miRNA-mediated inhibition of CD274 expression was accompanied by an increased T cell recognition. Furthermore, an inverse expression of three CD274-regulating miRNAs and CD274 was demonstrated in melanoma lesions. A CD274 miRNA score was generated, which was associated with disease progression and reduced survival of melanoma patients. Conclusions: These data revealed a novel mechanism that miRNAs targeting the CDS of immune checkpoint genes are functional, have prognostic relevance, and also the potential for the development of novel miRNA-based therapies

    Going means trouble and staying makes it double: the value of licensing recorded music online

    Get PDF
    This paper discusses whether a copyright compensation system (CCS) for recorded music—endowing private Internet subscribers with the right to download and use works in return for a fee—would be welfare increasing. It reports on the results of a discrete choice experiment conducted with a representative sample of the Dutch population consisting of 4986 participants. Under some conservative assumptions, we find that applied only to recorded music, a mandatory CCS could increase the welfare of rights holders and users in the Netherlands by over €600 million per year (over €35 per capita). This far exceeds current rights holder revenues from the market of recorded music of ca. €144 million per year. A monthly CCS fee of ca. €1.74 as a surcharge on Dutch Internet subscriptions would raise the same amount of revenues to rights holders as the current market for recorded music. With a voluntary CCS, the estimated welfare gains to users and rights holders are even greater for CCS fees below €20 on the user side. A voluntary CCS would also perform better in the long run, as it could retain a greater extent of market coordination. The results of our choice experiment indicate that a well-designed CCS for recorded music would simultaneously make users and rights holders better off. This result holds even if we correct for frequently observed rates of overestimation in contingent valuation studies

    Catabolic Ornithine Carbamoyltransferase Activity Facilitates Growth of Staphylococcus aureus in Defined Medium Lacking Glucose and Arginine

    Get PDF
    Previous studies have found that arginine biosynthesis in Staphylococcus aureus is repressed via carbon catabolite repression (CcpA), and proline is used as a precursor. Unexpectedly, however, robust growth of S. aureus is not observed in complete defined medium lacking both glucose and arginine (CDM-R). Mutants able to grow on agar-containing defined medium lacking arginine (CDM-R) were selected and found to contain mutations within ahrC, encoding the canonical arginine biosynthesis pathway repressor (AhrC), or single nucleotide polymorphisms (SNPs) upstream of the native arginine deiminase (ADI) operon arcA1B1D1C1. Reverse transcription-PCR (RT-PCR) studies found that mutations within ccpA or ahrC or SNPs identified upstream of arcA1B1D1C1 increased the transcription of both arcB1 and argGH, encoding ornithine carbamoyltransferase and argininosuccinate synthase/lyase, respectively, facilitating arginine biosynthesis. Furthermore, mutations within the AhrC homologue argR2 facilitated robust growth within CDM-R. Complementation with arcB1 or arcA1B1D1C1, but not argGH, rescued growth in CDM-R. Finally, supplementation of CDM-R with ornithine stimulated growth, as did mutations in genes (proC and rocA) that presumably increased the pyrroline-5-carboxylate and ornithine pools. Collectively, these data suggest that the transcriptional regulation of ornithine carbamoyltransferase and, in addition, the availability of intracellular ornithine pools regulate arginine biosynthesis in S. aureus in the absence of glucose. Surprisingly, ~50% of clinical S. aureus isolates were able to grow in CDM-R. These data suggest that S. aureus is selected to repress arginine biosynthesis in environments with or without glucose; however, mutants may be readily selected that facilitate arginine biosynthesis and growth in specific environments lacking arginine. IMPORTANCE Staphylococcus aureus can cause infection in virtually any niche of the human host, suggesting that it has significant metabolic versatility. Indeed, bioinformatic analysis suggests that it has the biosynthetic capability to synthesize all 20 amino acids. Paradoxically, however, it is conditionally auxotrophic for several amino acids, including arginine. Studies in our laboratory are designed to assess the biological function of amino acid auxotrophy in this significant pathogen. This study reveals that the metabolic block repressing arginine biosynthesis in media lacking glucose is the transcriptional repression of ornithine carbamoyltransferase encoded by arcB1 within the native arginine deiminase operon in addition to limited intracellular pools of ornithine. Surprisingly, approximately 50% of S. aureus clinical isolates can grow in media lacking arginine, suggesting that mutations are selected in S. aureus that allow growth in particular niches of the human host

    The Symptom Monitoring with Feedback Trial (SWIFT):protocol for a registry‑based cluster randomised controlled trial in haemodialysis

    Get PDF
    BACKGROUND: Kidney failure prevalence is increasing worldwide. Haemodialysis, peritoneal dialysis or kidney transplantation are undertaken to extend life with kidney failure. People receiving haemodialysis commonly experience fatigue, pain, nausea, cramping, itching, sleeping difficulties, anxiety and depression. This symptom burden contributes to poor health-related quality of life (QOL) and is a major reason for treatment withdrawal and death. The Symptom monitoring WIth Feedback Trial (SWIFT) will test the hypothesis that regular symptom monitoring with feedback to people receiving haemodialysis and their treating clinical team can improve QOL. METHODS: We are conducting an Australia and New Zealand Dialysis and Transplant (ANZDATA) registry-based cluster randomised controlled trial to determine the clinical- and cost-effectiveness at 12 months, of 3-monthly symptom monitoring using the Integrated Palliative Outcome Scale-Renal (IPOS-Renal) survey with clinician feedback, compared with usual care among adults treated with haemodialysis. Participants complete symptom scoring using a tablet, which are provided to participants and to clinicians. The trial aims to recruit 143 satellite haemodialysis centres, (up to 2400 participants). The primary outcome is change in health-related QOL, as measured by EuroQol 5-Dimension, 5-Level (EQ-5D-5L) instrument. Secondary outcomes include overall survival, symptom severity (including haemodialysis-associated fatigue), healthcare utilisation and cost-effectiveness. DISCUSSION: SWIFT is the first registry-based trial in the Australian haemodialysis population to investigate whether regular symptom monitoring with feedback to participants and clinicians improves QOL. SWIFT is embedded in the ANZDATA Registry facilitating pragmatic recruitment from public and private dialysis clinics, throughout Australia. SWIFT will inform future collection, storage and reporting of patient-reported outcome measures (PROMs) within a clinical quality registry. As the first trial to rigorously estimate the efficacy and cost-effectiveness of routine PROMs collection and reporting in haemodialysis units, SWIFT will provide invaluable information to health services, clinicians and researchers working to improve the lives of those with kidney failure. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001061921. Registered on 16 October 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06355-0

    Feasibility and acceptability of e-PROMs data capture and feedback among patients receiving haemodialysis in the Symptom monitoring WIth Feedback Trial (SWIFT) pilot: protocol for a qualitative study in Australia

    Get PDF
    INTRODUCTION: People receiving haemodialysis experience a high symptom burden and impaired quality of life. The use of patient-reported outcome measures (PROMs) is increasing in nephrology care, however their acceptability, utility and impacts are not well understood. METHODS AND ANALYSIS: We describe a protocol for a qualitative study to evaluate the feasibility and acceptability of electronic-PROMs (e-PROMs) data capture and feedback in haemodialysis following the pilot Symptom monitoring WIth Feedback Trial (SWIFT). SWIFT involves linkage of e-PROMs data, including symptoms and health-related quality of life, to the Australia and New Zealand Dialysis and Transplant Registry with feedback to patients' treating nephrologists and nurse unit managers. Focus groups and semistructured interviews will be conducted with nephrologists (n=15), dialysis nurses (n=24) and patients receiving haemodialysis (n=24) from six dialysis units in Australia. Question topics will include the technical and clinical feasibility and acceptability of e-PROMs reporting and feedback (including the barriers and enablers to uptake) and perceived impact on patient care and outcomes. Transcripts will be analysed thematically and guided by Normalisation Process Theory. ETHICS AND DISSEMINATION: Ethics approval was obtained from the relevant hospital Human Research Ethics Committees (HREC/18/CALHN/481; HREC/MML/54599). The findings from the SWIFT pilot and qualitative evaluation will inform the implementation of the SWIFT main trial, and more broadly, the use of e-PROMs in clinical settings and registries. TRIAL REGISTRATION NUMBER: ANZCTRN12618001976279.Emily Duncanson, Paul N Bennett, Andrea Viecelli, Kathryn Dansie, William Handke, Allison Ton

    Entrepreneurial orientation of traditional and modern cultural organisations: cases in George Town UNESCO World Heritage Site

    Get PDF
    George Town World Heritage Site in Penang, Malaysia is well-endowed with creative and cultural resources, and has recently witnessed a rise in relevant rise in creative and cultural activities. This study examines how 'innovation culture' is inculcated and embedded within two local organisations with distinct approaches to innovation. This examination adopts and adapts the concept of Entrepreneurial Orientation, using three constructs: i) innovativeness, ii) risk-taking and iii) pro-activeness. This study administered a purely qualitative research approach by conducting in-depth semi-structured interviews and archival study of the chosen case organisations and their networks. The novelty of this research resides in the choice of case study organisations chosen (i.e. traditional versus modern) where a comparative approach was used to compare and contrast innovation culture and gauge the extent upon which entrepreneurship orientation constructs are prevalent and thriving in these organisations. By documenting the linkages in their value chains, this study managed to understand their resulting social networks and whether such network fosters the incubation of an innovation cluster for the local creative and cultural sectors. This study concluded that traditional cultural organisations tend to be more cautious and even passive in their business approach and decision-making processes, while modern and newer cultural and creative organisations lean towards a more active and dynamic outlook, albeit sometimes constrained by lack of resources, i.e. funding and facilities, as well as impeded by the nature of their informality. These findings can contribute towards shaping pragmatic human resource and creative industry policies for city planners and policy makers, particularly in the George Town World Heritage Site, as well as serving as point of reference for other world heritage sites in the world

    Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Cardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic stroke from non-cardioembolic stroke (atherothrombotic stroke and lacunar stroke). In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic stroke or non-cardioembolic stroke, and assessed the prediction factors of plasma brain natriuretic peptide and whether we could differentiate between stroke subtypes on the basis of plasma brain natriuretic peptide concentrations in addition to patient's clinical variables.</p> <p>Methods</p> <p>Our patient cohort consisted of 131 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005 to December 31, 2007. The mean age of patients (43 females, 88 males) was 69.6 ± 10.1 years. Sixty-two patients had cardioembolic stroke; the remaining 69 patients had non-cardioembolic stroke (including atherothrombotic stroke, lacunar stroke, or the other). Clinical variables and the plasma brain natriuretic peptide were evaluated in all patients.</p> <p>Results</p> <p>Plasma brain natriuretic peptide was linearly associated with atrial fibrillation, heart failure, chronic renal failure, and left atrial diameter, independently (F<sub>4,126 </sub>= 27.6, p < 0.0001; adjusted R<sup>2 </sup>= 0.45). Furthermore, atrial fibrillation, mitral regurgitation, plasma brain natriuretic peptide (> 77 pg/ml), and left atrial diameter (> 36 mm) were statistically significant independent predictors of cardioembolic stroke in the multivariable setting (Χ<sup>2 </sup>= 127.5, p < 0.001).</p> <p>Conclusion</p> <p>It was suggested that cardioembolic stroke was strongly predicted with atrial fibrillation and plasma brain natriuretic peptide. Plasma brain natriuretic peptide can be a surrogate marker for cardioembolic stroke.</p

    Lack of association between right-to-left shunt and cerebral ischemia after adjustment for gender and age

    Get PDF
    <p>Abstract</p> <p>Introduction</p> <p>A number of studies has addressed the possible association between patent foramen ovale (PFO) and stroke. However, the role of PFO in the pathogenesis of cerebral ischemia has remained controversial and most studies did not analyze patient subgroups stratified for gender, age and origin of stroke.</p> <p>Methods</p> <p>To address the role of PFO for the occurrence of cerebral ischemia, we investigated the prevalence of right-to-left shunt in a large group of patients with acute stroke or TIA. 763 consecutive patients admitted to our hospital with cerebral ischemia were analyzed. All patients were screened for the presence of PFO by contrast-enhanced transcranial Doppler sonography at rest and during Valsalva maneuver. Subgroup analyses were performed in patients stratified for gender, age and origin of stroke.</p> <p>Results</p> <p>A right-to-left shunt was detected in 140 (28%) male and in 114 (42%) female patients during Valsalva maneuver, and in 66 (13%) and 44 (16%) at rest respectively. Patients with right-to-left shunt were younger than those without (<it>P </it>< 0.001). PFO was associated with stroke of unknown origin in male (<it>P </it>= 0.001) but not female patients (<it>P </it>> 0.05). After adjusting for age no significant association between PFO and stroke of unknown origin was found in either group.</p> <p>Conclusion</p> <p>Our findings argue against paradoxical embolization as a major cause of cerebral ischemia in patients with right-to-left shunt. Our data demonstrate substantial gender-and age-related differences that should be taken into account in future studies.</p
    corecore