81 research outputs found

    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

    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

    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

    Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

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    BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≄100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≀0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

    From the Sum of Near-Zero Energy Buildings to the Whole of a Near-Zero Energy Housing Settlement: The Role of Communal Spaces in Performance-Driven Design

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    Almost a century ago Modernism challenged the structure of the city and reshaped its physical space in order to, amongst other things, accommodate new transportation infrastructure and road networks proclaiming the,nowadays much-debated ‘scientificated’ pursuit of efficiency for the city. This transformation has had a great impact on the way humans still design, move in, occupy and experience the city. Today major cities in Europe, such as Paris and London, are considering banning vehicles from their historic centers. In parallel, significant effort is currently underway internationally by designers, architects, and engineers to integrate innovative technologies and sophisticated solutions for energy production, management, and storage, as well as for efficient energy consumption, into the architecture of buildings. In general, this effort seeks for new technologies and design methods (e.g., DesignBuilder with EnergyPlus simulation engine; Rhicoceros3D with Grasshopper plugin and Ecotect, Radiance and EnergyPlus tools) that would enable a holistic approach to the spatial design of Near-Zero Energy buildings, so that their ecological benefits are an added value to the architectural design and a building’s visual, and material, impact on its surrounding space. The paper inquires how the integration of such technological infrastructure and performance-orientated interfaces changes yet again the structure and form of cities, and to what extent it safeguards social rights and enables equal access to common resources. Drawing from preliminary results and initial considerations of ongoing research that involve the construction of four innovative NZE settlements across Europe, in the context of the EU-funded ZERO-PLUS project, this paper discusses the integration of novel infrastructure in communal spaces of these settlements. In doing so, it contributes to the debate about smart communities and their role in the sustainable management of housing developments and settlements that are designed and developed with the concept of smart territories

    Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn’s disease

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    Background: Fistulae are a troublesome complication of Crohn’s disease but little is known of the final effector molecules responsible for matrix degradation. Although matrix metalloproteinases (MMPs) have been strongly implicated in tissue injury in Crohn’s disease, their role in fistula formation is unknown. Aim: To determine the expression pattern of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in fistulae of patients with Crohn’s disease. Patients and methods: Resected fistula specimens were obtained from patients with Crohn’s disease (n = 11) and classified according to the predominant histological features—that is, acute versus chronic inflammation. Patients with fistulae due to other diseases (n = 9) and normal colon (n = 5) served as controls. MMP and TIMP protein expression was measured by single or double labelled immunohistochemistry, and mRNA expression by in situ hybridisation. MMP activity was measured by gelatin zymography. Results: Compared with normal colon, strong MMP-3 expression was consistently observed in fistulae in Crohn’s disease, irrespective of the stage of inflammatory activity. MMP-3 transcripts and protein were localised in large mononuclear cells and fibroblasts. MMP-9 transcripts and protein were expressed in granulocytes and only in fistulae with acute inflammation. Staining for MMP-1 and MMP-7 was weak and negative for MMP-10, whereas MMP-2 was equally expressed in normal colon and fistulae. TIMP-1, TIMP-2, and TIMP-3 expression was low in all samples. Similar expression patterns were found in fistulae of the disease control group. Fistulae also expressed active MMP-2 and MMP-9, as measured by gelatin zymography. Conclusion: MMP-3 and MMP-9 are markedly upregulated in intestinal fistulae and may contribute to fistula formation through degradation of the extracellular matrix, irrespective of the underlying disease process
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