110 research outputs found

    Spin wave spectrum of the quantum ferromagnet on the pyrochlore lattice Lu2V2O7

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    Neutron inelastic scattering has been used to probe the spin dynamics of the quantum (S=1/2) ferromagnet on the pyrochlore lattice Lu2V2O7. Well-defined spin waves are observed at all energies and wavevectors, allowing us to determine the parameters of the Hamiltonian of the system. The data are found to be in excellent overall agreement with a minimal model that includes a nearest- neighbour Heisenberg exchange J = 8:22(2) meV and a Dzyaloshinskii-Moriya interaction (DMI) D =1:5(1) meV. The large DMI term revealed by our study is broadly consistent with the model developed by Onose et al. to explain the magnon Hall effect they observed in Lu2V2O7 [1], although our ratio of D=J = 0:18(1) is roughly half of their value and three times larger than calculated by ab initio methods [2].Comment: 5 pages, 4 figure

    Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus

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    Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These-originally β-cell secretory products-extracellular aggregates are cytotoxic for insulin-producing β-cells and are associated with β-cell loss and inflammation in T2DM advanced stages. Due to the absence of T2DM preventive medicaments and the presence of only symptomatic drugs acting towards increasing hormone secretion and action, we aimed at establishing a novel disease-modifying therapy targeting the cytotoxic IAPP deposits in order to prevent the development of T2DM. We generated a vaccine based on virus-like particles (VLPs), devoid of genomic material, coupled to IAPP peptides inducing specific antibodies against aggregated, but not monomeric IAPP. Using a mouse model of islet amyloidosis, we demonstrate in vivo that our vaccine induced a potent antibody response against aggregated, but not soluble IAPP, strikingly preventing IAPP depositions, delaying onset of hyperglycemia and the induction of the associated pro-inflammatory cytokine Interleukin 1β (IL-1β). We offer the first cost-effective and safe disease-modifying approach targeting islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing physiological IAPP function.These studies were funded by a project grant from the Swiss National Foundation (SNF). We acknowledge the technical assistance of Sydney W. Pence and Faith Slubowski at the Institute of Veterinary Physiology, University of Zßrich. We appreciate the kind possibility given by Nanolive (Lausanne, Switzerland) for the opportunity and the collaborative acquisition of tomographic pictures.S

    Types, obstacles and sources of empowerment in co-design: the role of shared material objects and processes

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    Co-design is intrinsically linked to the notion of empowerment, however little research has focussed specifically on understanding the types, obstacles and sources of empowerment in co-design. This paper combines theoretical investigations with observations derived from co-designed research by academic and non-academic partners to explore these issues, in particular, the role of shared material objects and processes in supporting empowerment during co-design. The paper uses the notions of ‘power over,’ ‘power to’, ‘power with’ and ‘power within’ to tease out different aspects of empowerment, and draws on empirical observations to determine different obstacles and sources associated with each. The study therefore makes a theoretical contribution to the understanding of co-design as an empowerment process and should be useful for design researchers undertaking co-design projects with non-experts

    Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by conjugation to virus-like particles

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    BACKGROUND: Tumour cell lysates are an excellent source of many defined and undefined tumour antigens and have been used clinically in immunotherapeutic regimes but with limited success. METHODS: We conjugated Mel888 melanoma lysates to rabbit haemorrhagic disease virus virus-like particles (VLP), which can act as vehicles to deliver multiple tumour epitopes to dendritic cells (DC) to effectively activate antitumour responses. RESULTS: Virus-like particles did not stimulate the phenotypic maturation of DC although, the conjugation of lysates to VLP (VLP-lysate) did overcome lysate-induced suppression of DC activation. Lysate-conjugated VLP enhanced delivery of antigenic proteins to DC, while the co-delivery of VLP-lysates with OK432 resulted in cross-priming of naĂŻve T cells, with expansion of a MART1(+) population of CD8(+) T cells and generation of a specific cytotoxic response against Mel888 tumour cell targets. The responses generated with VLP-lysate and OK432 were superior to those stimulated by unconjugated lysate with OK432. CONCLUSION: Collectively, these results show that the combination of VLP-lysate with OK432 delivered to DC overcomes the suppressive effects of lysates, and enables priming of naĂŻve T cells with superior ability to specifically kill their target tumour cells

    Internet use, needs and expectations of web-based information and communication in childbearing women with type 1 diabetes

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    <p>Abstract</p> <p>Background</p> <p>In the childbearing period women use the internet both to seek information and as an important source of communication. For women with type 1 diabetes, pregnancy and early motherhood constitute a more complex situation than for women in general. This implies need for support from various professionals and a way of bridging any discontinuity in care would be to develop a website providing complementary social support and information. The objective of this study was to explore internet use, needs, and expectations regarding web-based information and communication in childbearing women with type 1 diabetes.</p> <p>Methods</p> <p>Data were collected via a web-based survey with an explorative and descriptive design, in which 105 of 139 eligible mothers with type 1 diabetes and recent childbearing experience participated. The data were analyzed with descriptive and analytical statistics, and open answers with a directed content analysis.</p> <p>Results</p> <p>Of the 105 women, 22% never used the internet to search for information concerning pregnancy, childbirth, and parenthood. 12% searched for information every day, 29% one or more times a week, and 38% one or more times a month. Of the women 44% declared themselves to be passive participants on social websites, and 45% to be active participants. 45% had specific expectations of web-based support directed towards childbearing, especially those with higher educational level (<it>P </it>= .01). Expectations of instrumental and informational support included an expert-controlled website with reliable, updated, and information focused on childbearing and diabetes, improved access to diabetes care professionals and alternative ways to communicate and to receive childbearing-related support. The women also asked for online technical devices to manage the frequent monitoring of blood glucose during pregnancy. Informal, emotional, and appraisal support from women in similar situations was suggested as a way to provide an arena for belonging instead of creating feelings of alienation.</p> <p>Conclusions</p> <p>Our results add important knowledge about the web-based needs of women with type 1 diabetes in relation to childbearing. This user directed study indicates specific areas of development for the provision of effective web-based support that includes facilities for reliable information, interactive support and social networking in this population.</p

    Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis.

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    BACKGROUND Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA. AIM To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS. METHODS Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded. RESULTS At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month. CONCLUSIONS The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427

    Microneedles: A New Frontier in Nanomedicine Delivery

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    This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN
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