73 research outputs found

    Connecting the Edges: A Universal, Mobile-Centric, and Opportunistic Communications Architecture

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    The Internet has crossed new frontiers with access to it getting faster and cheaper. Considering that the architectural foundations of today's Internet were laid more than three decades ago, the Internet has done remarkably well until today coping with the growing demand. However, the future Internet architecture is expected to support not only the ever growing number of users and devices, but also a diverse set of new applications and services. Departing from the traditional host-centric access paradigm, where access to a desired content is mapped to its location, an information-centric model enables the association of access to a desired content with the content itself, irrespective of the location where it is being held. UMOBILE tailors the information-centric communication model to meet the requirements of opportunistic communications, integrating those connectivity approaches into a single architecture. By pushing services near the edge of the network, such an architecture can pervasively operate in any networking environment and allows for the development of innovative applications, providing access to data independent of the level of end-to-end connectivity availability

    Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease

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    Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt-Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an end, thanks to lessons learnt from past infection sources that promoted new prion prevention and decontamination protocols. At this point, we sought to characterise the biomarker profile of iCJD and compare it to that of sporadic CJD (sCJD) for determining the value of available diagnostic tools in promptly recognising iCJD cases. To that end, we collected 23 iCJD samples from seven national CJD surveillance centres and analysed the electroencephalogram and neuroimaging data together with a panel of seven CSF biomarkers: 14-3-3, total tau, phosphorylated/total tau ratio, alpha-synuclein, neurofilament light, YKL-40, and real-time quaking induced conversion of prion protein. Using the cut-off values established for sCJD, we found the sensitivities of these biomarkers for iCJD to be similar to those described for sCJD. Given the limited relevant information on this issue to date, the present study validates the use of current sCJD biomarkers for the diagnosis of future iCJD cases.This research was funded by the Instituto Carlos III (grants CP/00041 and PI19/00144) and by the Fundació La Marató de TV3 (201821‐30‐31‐32) to FL and by the Robert Koch Institute through funds from the Federal Ministry of Health (grant No, 1369‐341) to IZ. This project was also funded at 65% by the Fondo Europeo de Desarrollo Regional (FEDER) through the Interreg V‐A España‐Francia‐Andorra (POCTEFA 2014‐2020) programme. SJC is funded in part by a NHMRC Practitioner Fellowship (identification #APP1105784).S

    Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study

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    Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms. Methods: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country. Findings: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10-15; heterozygous model p=1·01 × 10-135), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions. Interpretation: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders. Funding: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust

    The nature and purpose of the DBA: A case for clarity and quality control

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    Purpose - To explore the nature (component parts, degree structure) and purpose (intended outcomes) of the Doctor of Business Administration (DBA) degree, identifying the strengths and weaknesses of the degree as they stand presently, using Australian experience. Design/methodology/approach - A review of DBA programme offerings in Australia identified commonalities and differences in these offerings, and provided information necessary to propose strategic and theoretical implications of DBA education. Findings - The paper demonstrates areas of confusion surrounding the purpose and nature of the DBA degree, especially as a research degree in comparison to the PhD. It concludes that quality controls are needed to ensure that this growing addition to management education adds to, and aids, the goal of strengthening management research, in ways that link theoretical insights with management practice. Research limitations/implications - Theoretical and practical implications of the DBA degree are offered, as well as the extent to which the DBA addresses the educational needs of students and its benefits to the university. Practical implications - The paper provides data useful to administrators interested in establishing a DBA degree in their institution, for researchers wishing to further explore and contribute to the discourse regarding the calibre and content of DBA degrees, and for students wishing to learn more about the fundamental differences between the PhD and the DBA. Originality/value - This paper provides new information about the way the DBA degree is developing in an Australian context, and offers advice on issues that need attention in order to further ground the DBA in a combined research and practitioner ethic

    Work Alienation: A Relevant Theoretical Framework for Examining Management Practices?

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    This paper discusses the relevance of a work alienation framework for examining management practices within large Australian organisations. A review of the relevant literature is used to build a theoretical framework of work alienation grounded in a radical-humanist work paradigm. The paper concludes by highlighting resistance to change problems associated with unitarist management control mechanisms that deny employees autonomy, participation and self-expression in the workplace
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