432 research outputs found

    E-government challenges – exploring inter-organisational aspects of e-service development

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    In this paper we are applying inter-organizational concepts from the industrial/business network approach on empirical findings from an e-government case, in order to describe and better understand challenges in one-stop government e-service development. We analyze our case by using concepts that characterize an inter-organizational relationship in terms of its level of continuity, complexity, symmetry, informality, and its dimensions (links, bonds, and ties). The purpose of the paper is to explore how these theoretical concepts can help us focus on certain aspects of e-service development challenges. The empirical findings are collected within an on-going action research project for e-service development in the public sector in Sweden. The aim of the project is to develop one-stop government e-services for driver’s license matters as well as a web-based portal where these e-services and information about the driver’s license process will be easily accessible. Our conclusions are that the theoretical concepts helped us reach further understanding of the empirical case. In the spirit of the network approach, we focused on the present situation and been able to give a rather detailed and fine-grained picture of the problems and challenges in this context

    The potential of vehicle and road infrastructure interventions in fatal bicyclist accidents on Swedish roads—What can in-depth studies tell us?

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    Objective: The objective of this article is to describe the characteristics of fatal crashes with bicyclists on Swedish roads in rural and urban areas and to investigate the potential of bicycle helmets and different vehicle and road infrastructure interventions to prevent them. The study has a comprehensive approach to provide road authorities and vehicle manufacturers with recommendations for future priorities. Methods: The Swedish Transport Administration’s (STA) in-depth database of fatal crashes was used for case-by-case analysis of fatal cycling accidents (2006–2016) on rural (n = 82) and urban (n = 102) roads. The database consists of information from the police, medical journals, autopsy reports, accident analyses performed by STA, and witness statements. The potential of helmet use and various vehicle and road infrastructure safety interventions was determined retrospectively for each case by analyzing the chain of events leading to the fatality. The potential of vehicle safety countermeasures was analyzed based on prognoses on their implementation rates in the Swedish vehicle fleet. Results: The most common accident scenario on rural roads was that the bicyclist was struck while cycling along the side of the road. On urban roads, the majority of accidents occurred in intersections. Most accidents involved a passenger car, but heavy trucks were also common, especially in urban areas. Most accidents occurred in daylight conditions (73%). Almost half (46%) of nonhelmeted bicyclists would have survived with a helmet. It was assessed that nearly 60% of the fatal accidents could be addressed by advanced vehicle safety technologies, especially autonomous emergency braking with the ability to detect bicyclists. With regard to interventions in the road infrastructure, separated paths for bicyclists and bicycle crossings with speed calming measures were found to have the greatest safety potential. Results indicated that 91% of fatally injured bicyclists could potentially be saved with known techniques. However, it will take a long time for such technologies to be widespread. Conclusions: The majority of fatally injured bicyclists studied could potentially be saved with known techniques. A speedy implementation of important vehicle safety systems is recommended. A fast introduction of effective interventions in the road infrastructure is also necessary, preferably with a plan for prioritization

    Proposed protective mechanism of the pancreas in the rat

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    <p>Abstract</p> <p>Background</p> <p>Heparan sulphate is known to have various functions in the animal body, including surveillance of tissue integrity. Administered intraperitoneally, it induces a systemic inflammatory response syndrome and when given locally in the pancreas it initiates a protective inflammatory response. The aim of the present study was to investigate the underlying mechanisms behind cell recruitment following intra-ductal infusion of heparan sulphate.</p> <p>Methods</p> <p>Rats were subjected to intraductal-infusion of heparan sulphate, lipopolysaccharide and phosphate buffered saline into the pancreas. Pancreatic tissue was harvested 1, 3, 6, 9 or 48 hours after infusion and stained immunohistochemically for myeloperoxidase, ED-1, CINC-1 and MCP-1, as well as using eosin hematoxylin staining. Furthermore, MPO activity and MCP-1 and CINC-1 concentrations of tissue homogenates were measured. All differences were analyzed statistically using the Mann-Whitney U-test.</p> <p>Results</p> <p>During HS infusion, a rapid influx of macrophages/monocytes, as visualized as ED-1 positive cells, was seen reaching a maximum at 6 hours. After 48 hours, the same levels of ED-1 positive cells were noted in the pancreatic tissue, but with different location and morphology. Increased neutrophil numbers of heparan sulphate treated animals compared to control could be detected only 9 hours after infusion. The number of neutrophils was lower than the number of ED-1 positive cells. On the contrary, LPS infusion caused increased neutrophil numbers to a larger extent than heparan sulphate. Furthermore, this accumulation of neutrophils preceded the infiltration of ED-1 positive cells. Chemokine expression correlates very well to the cell infiltrate. MCP-1 was evident in the ductal cells of both groups early on. MCP-1 preceded monocyte infiltration in both groups, while the CINC-1 increase was only noticeable in the LPS group.</p> <p>Conclusions</p> <p>Our data suggest that heparan and LPS both induce host defense reactions, though by using different mechanisms of cell-recruitment. This implies that the etiology of pancreatic inflammation may influence how the subsequent events will develop.</p

    Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties11This review is dedicated to the memory of Professor Lars Ernster.

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    AbstractTranshydrogenase couples the stereospecific and reversible transfer of hydride equivalents from NADH to NADP+ to the translocation of proton across the inner membrane in mitochondria and the cytoplasmic membrane in bacteria. Like all transhydrogenases, the Escherichia coli enzyme is composed of three domains. Domains I and III protrude from the membrane and contain the binding site for NAD(H) and NADP(H), respectively. Domain II spans the membrane and constitutes at least partly the proton translocating pathway. Three-dimensional models of the hydrophilic domains I and III deduced from crystallographic and NMR data and a new topology of domain II are presented. The new information obtained from the structures and the numerous mutation studies strengthen the proposition of a binding change mechanism, as a way to couple the reduction of NADP+ by NADH to proton translocation and occurring mainly at the level of the NADP(H) binding site

    Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.

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    The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer

    Identification of a serum biomarker signature associated with metastatic prostate cancer

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    Purpose: Improved early diagnosis and determination of aggressiveness of prostate cancer (PC) is important to select suitable treatment options and to decrease over-treatment. The conventional marker is total prostate specific antigen (PSA) levels in blood, but lacks specificity and ability to accurately discriminate indolent from aggressive disease. Experimental design: In this study, we sought to identify a serum biomarker signature associated with metastatic PC. We measured 157 analytes in 363 serum samples from healthy subjects, patients with non-metastatic PC and patients with metastatic PC, using a recombinant antibody microarray. Results: A signature consisting of 69 proteins differentiating metastatic PC patients from healthy controls was identified. Conclusions and clinical relevance: The clinical value of this biomarker signature requires validation in larger independent patient cohorts before providing a new prospect for detection of metastatic PC

    Suspicion and treatment of severe sepsis. An overview of the prehospital chain of care

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    Sepsis is a life-threatening condition where the risk of death has been reported to be even higher than that associated with the major complications of atherosclerosis, i.e. myocardial infarction and stroke. In all three conditions, early treatment could limit organ dysfunction and thereby improve the prognosis
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