158 research outputs found

    Soluble interleukin-2 receptors in ulcerative colitis

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    T-Cell activation results in the release or shedding of a soluble form (45 kDa) of the cellular (55 kDa) low-affinity interleukin-2 receptor (α-chain) (slL-2R). The present study was performed to investigate if the serum concentration of sIL-2R is a marker of disease activity in patients with ulcerative colitis (UC), a chronic inflammatory bowel disease. Twenty-seven UC patients (about half of them in remission) and 13 healthy volunteers were studied, sIL-2R concentrations were measured by an enzyme-linked immunosorbent assay, and significantly elevated median sIL-2R values were found in clinically active UC (150 pg/ml; range 100–420), compared to inactive UC (145 pg/ml; range 110–255), and healthy controls (110 pg/ml; range 80–165) (p < 0.01). There was no correlation between sIL-2R concentrations and extent of the disease. Due to the overlap of serum sIL-2R concentrations between different disease stages and controls, the general diagnostic value seems to be limited. However, since slL-2R release is an IL-2 dependent phenomenon, we conclude that the demonstration of increased serum sIL-2R concentrations in UC suggests the existence of an enhanced T-cell activation in vivo in this disease. Further longitudinal studies are required to elucidate if repeated measurements of sIL-2R levels provide an additional way of monitoring UC disease activity in individual patients

    DIGISER. Digital Innovation in Governance and Public Service Provision

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    Digital Innovation Challenges In view of the increasingly intense pressures on the public sector to address the challenges of our time, governments and other public entities are gradually adopting digital innovation, seeking to promote quality public services. Digital technologies and capabilities create opportunities to re-organise public service inno- vation and delivery in ways that reduce cost and increase quality, proactiveness and citizen-centricity. Multilevel governance, networks and other collaboration systems (at local, regional, national and interna- tional level) are gaining importance as key drivers of this process of digital innovation and transformation. The link to the innovation ecosystem, including all sectors of activity, both private and public (e.g., academia, industry, business, citizens and governments) appears as fundamental in all phases of the creation, devel- opment, implementation and maintenance of public services and policy making. Information and communi- cation technologies are conceived as essential elements to support the creation and sustainability of these collaboration processes. In an era in which information gains relevance in the management of the territory and allows new power relations, the expectations of citizens are increasingly demanding and specific. Considering the develop- ments of recent years, such as the economic, social and health crises, the pressure placed on the resolution of global challenges is progressively transferred to the scope of cities. There are several elements that con- tribute to the importance of cities in the digital innovation transformation process namely buying- power, being closer to citizens and being able to work across different sectors. In fact, urban territories increasingly represent a greater number of citizens - in Europe, for example, they correspond to 75% of the population - have greater autonomy in management, worldwide they contribute to 80% of the global GDP and have the potential to provide a major contribution to the resolution of global challenges. The balance between change (promoted by the digital innovation strategies) and stability (driven by organi- sational inertia) needs to be handled carefully. The transformation process has to be based on a long-term strategy and to occur in a sustainable way, by focusing on learning experiences and knowledge and tech- nology transfer, while being sensitive to the local context to ensure improvement. At the European level, the Digital Transition has been considered a main goal for the next decade. The EU launched the European Green Deal and Europe Fit for the Digital Age, a twin initiative, which links green and digital transition. The vision for the EU ́s digital decade is reflected in the Digital Compass 2030 and includes 4 cardinal points: skills, government, infrastructure and Business. With the aim of having 100% of the key public services online by 2030, the digital compass ensures that digital will contribute in a positive way to improve citizens quality of life while reducing the resources spent. To support this vision, and by understanding the importance of community-led data-driven solutions and the potential of collaborative ap- proaches, several initiatives are being implemented. The Living-in.EU movement, for example, points out the European Way’ where multi-level governance and co-creation processes support the development of a cohesive digital Europe in the path towards digital transition. Another initiative contributing to this strategy is promoted by Open &amp; Agile Smart Cities which is connecting cities through Minimal Interoperability Mech- anisms (MIMs) - “a set of practical capabilities based on open technical specifications that allow cities and communities to replicate and scale solutions globally”. The MIMs contribute to the creation of the European Single Market by providing a common technical ground for the procurement and deployment of urban data platforms and end-to-end solutions in cities

    HCI policy and the smart city

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    While the idea of the ‘Smart City’ has attracted increasing attention from academia, industry, and government this interest has largely had a technical and technological focus. This paper identifies some of the important political and policy challenges facing the idea, the discourse, of a ‘smart city’ as a means to optimise HCI input into the ‘smart city’ debate. It then addresses that gap by detailing a research project that explored how experts in smart city research and development in the UK context responded to this policy challenge. Experts were asked questions regarding their prior experience with the “smart city”, their understandings of what it means for a city to be smart, and what policy potentials they've recognised in the smart city. The paper analyses and offers a synthesis of the responses collected throughout the research with the current policies concerning various smart city proximity, thereby providing a critical assessment of the values underlying the smart city. The paper aims to explore and present some of the policy possibilities for UK smart cities that are potentially useful for politicians, policy makers, planners, academics, and technology companies. I believe that these perspectives for policy development can be used to inform responsible development, spatially and socially inclusive technologies, and ultimately more resilient and liveable cities

    Tension Space Analysis: Exploring Community Requirements for Networked Urban Screens

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    This paper draws on the design process, implementation and early evaluation results of an urban screens network to highlight the tensions that emerge at the boundary between the technical and social aspects of design. While public interactive screens in urban spaces are widely researched, the newly emerging networks of such screens present fresh challenges. Researchers wishing to be led by a diverse user community may find that the priorities of some users, directly oppose the wishes of others. Previous literature suggests such tensions can be handled by ‘goal balancing’, where all requirements are reduced down to one set of essential, implementable attributes. Contrasting this, this paper’s contribution is ‘Tension Space Analysis’, which broadens and extends existing work on Design Tensions. It includes new domains, new representational methods and offers a view on how to best reflect conflicting community requirements in some aspects or features of the design

    On the Action of Cyclosporine A, Rapamycin and Tacrolimus on M. avium Including Subspecies paratuberculosis

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    BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. Recently the "immuno-modulators" methotrexate, azathioprine and 6-MP and the "anti-inflammatory" 5-ASA have been shown to inhibit MAP growth in vitro. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. The "immunosuppressants" Cyclosporine A, Rapamycin and Tacrolimus (FK 506) treat a variety of "autoimmune" and "inflammatory" diseases. Rapamycin and Tacrolimus are macrolides. We hypothesized that their mode of action may simply be to inhibit MAP growth. METHODOLOGY: The effect on radiometric MAP (14)CO(2) growth kinetics of Cyclosporine A, Rapamycin and Tacrolimus on MAP cultured from humans (Dominic & UCF 4) or ruminants (ATCC 19698 & 303) and M. avium subspecies avium (ATCC 25291 & 101) are presented as "percent decrease in cumulative GI" (%-DeltacGI.) PRINCIPAL FINDINGS: The positive control clofazimine has 99%-DeltacGI at 0.5 microg/ml (Dominic). Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immunosuppressants. Cyclosporine has 97%-DeltacGI by 32 microg/ml (Dominic), Rapamycin has 74%-DeltacGI by 64 microg/ml (UCF 4) and Tacrolimus 43%-DeltacGI by 64 microg/ml (UCF 4) CONCLUSIONS: We show heretofore-undescribed inhibition of MAP growth in vitro by "immunosuppressants;" the cyclic undecapeptide Cyclosporine A, and the macrolides Rapamycin and Tacrolimus. These data are compatible with our thesis that, unknowingly, the medical profession has been treating MAP infections since 1942 when 5-ASA and subsequently azathioprine, 6-MP and methotrexate were introduced in the therapy of some "autoimmune" and "inflammatory" diseases

    IL-1ÎČ Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity.

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    Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1ÎČ in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1ÎČ (IL-1ÎČ(-/-)), or treated with the soluble IL-1ÎČR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1ÎČ acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1ÎČ that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity

    Speaker- versus listener-oriented disfluency: A re-examination of arguments and assumptions from autism spectrum disorder

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    We re-evaluate conclusions about disfluency production in high-functioning forms of autism spectrum disorder (HFA). Previous studies examined individuals with HFA to address a theoretical question regarding speaker- and listener-oriented disfluencies. Individuals with HFA tend to be self-centric and have poor pragmatic language skills, and should be less likely to produce listener-oriented disfluency. However, previous studies did not account for individual differences variables that affect disfluency. We show that both matched and unmatched controls produce fewer repairs than individuals with HFA. For silent pauses, there was no difference between matched controls and HFA, but both groups produced more than unmatched controls. These results identify limitations in prior research and shed light on the relationship between autism spectrum disorders and disfluent speech
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