113 research outputs found

    Business IT Alignment through the Lens of Complexity Science

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    Business IT alignment has been a top concern for academics and corporate managers for over 30 years. Despite a rich literature, it is still far from been an achieved objective in companies. Leveraging on the similarities between Information and Complex Systems, researchers have recently adopted a new perspective to study Information Systems and their alignment with business. The present study is based on an extensive literature review that spans three domains of research: Information Systems, Complexity Science, and Organization Science. The paper proposes to contribute to the study and implementation of alignment by presenting a classification framework for the different alignment approaches exploiting methods derived from Complexity Science. Four types of approaches to alignment are identified and for each of them the potential contribution to alignment dimensions is discussed

    IS Architecture Complexity Dynamics in M&A: Does Consolidation Reduce Complexity?

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    In this paper we aim to improve our understanding of the dynamics of IS architecture complexity (i.e, the change in this complexity over time) during the execution of a consolidation IS integration strategy (IIS). Based on two case studies, we find that unexpected levels of complexity emerge during IIS execution because of an underestimation of requisite complexity and an overestimation of the potential to reduce complexity. Our analysis shows that increased complexity is due to the fact that the intended consolidation IIS is only partially executed, and to increasingly emergent IIS execution. Additionally, we find that while complexity was reduced at the portfolio level, at more detailed levels of observation complexity was actually increased. Our paper contributes to knowledge in the field by providing a deeper insight into IS architecture complexity dynamics during the execution of a consolidation IIS, and the concept of IS architecture complexity in general

    IS Antagonism: Explaining Negative Value Creation from IS Integration in M&A

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    IS integration problems are often an important determinant of negative value creation in Mergers and Acquisitions. To date, these problems are commonly attributed to mis-aligned Business and IS Integration Strategies, flawed preparation or execution or negative synergies, but the role of IS itself is underemphasized. Based on a case study and expert interviews, we propose a theory addressing this issue. Our explanation focuses on the concept of IS Antagonism, referring to the destructive interaction between previously independent information systems, which occurs when these are operationally combined. This concept offers novel explanations beyond strategic misalignment and considers the nature of the information systems themselves in the integration phase. IS antagonism is omni present in M&A, which has the practical implication that we need to account for its value destructing characteristics in pre-merger synergy predictions and by securing necessary IS resources to mitigate during execution

    Free-standing nanolayers based on Ru silicide formation on Si(100)

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    Free-standing layers of nanoscale thickness are essential in numerous applications but challenging to fabricate for all but a small selection of materials. We report a versatile, chemical-free pathway of exfoliating centimeter-sized free-standing nanolayers from Si(100) with native oxide based on the spontaneous delamination of thin Ru and Ru-based films upon annealing at temperatures as low as 400 °C. Combining results from X-ray photoelectron spectroscopy (XPS), and transmission and scanning electron microscopy (TEM, SEM), we identify that the element Ru, a thin SiO2 layer, and the Si(100) substrate are essential ingredients for the delamination and propose a stress-based mechanism to explain the effect. The diffusion of Si into the layer upon annealing leads to the formation of a Ru-Si compound at the thin-film side of the Ru/Si(100) interface and pyramidal cavities in the Si(100) substrate. Moreover, the uptake of Si results in an increase in layer thickness and the buildup of in-plane compressive stress, which is reduced by local buckling and finally by the separation of the full layer from the substrate at the SiO2-Si(100) interface. The use of a thin Ru-buffer layer allows us to apply this delamination process to produce free-standing nanolayers of Mo and HfMoNbTiZr in this simple, chemical-free, and vacuum-compatible manner. These results indicate the potential of the reported effect for the fabrication of free-standing layers using a wide range of compositions, deposition techniques, and growth conditions below the onset temperature of delamination

    Lack of virological and serological evidence for continued circulation of highly pathogenic avian influenza H5N8 virus in wild birds in the Netherlands, 14 November 2014 to 31 January 2016

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    In 2014, H5N8 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses of the A/Goose/ Guangdong/1/1996 lineage emerged in poultry and wild birds in Asia, Europe and North America. Here, wild birds were extensively investigated in the Netherlands for HPAI H5N8 virus (real-time polymerase chain reaction targeting the matrix and H5 gene) and antibody detection (haemagglutination inhibition and virus neutralisation assays) before, during and after the first virus detection in Europe in late 2014. Between 21 February 2015 and 31 January 2016, 7,337 bird samples were tested for the virus. One HPAI H5N8 virus-infected Eurasian wigeon (Anas penelope) sampled on 25 February 2015 was detected. Serological assays were performed on 1,443 samples, including 149 collected between 2007 and 2013, 945 between 14 November 2014 and 13 May 2015, and 349 between 1 September and 31 December 2015. Antibodies specific for HPAI H5 clade 2.3.4.4 were absent in wild bird sera obtained before 2014 and present in sera collected during and after the HPAI H5N8 emergence in Europe, with antibody incidence declining after the 2014/15 winter. Our results indicate that the HPAI H5N8 virus has not continued to circulate extensively in wild bird populations since the 2014/15 winter and that independent maintenance of the virus in these populations appears unlikely

    Agreement of general practitioners with the guideline-based stepped-care strategy for patients with osteoarthritis of the hip or knee: A cross-sectional study

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    Background: To improve the management of hip or knee osteoarthritis (OA), a multidisciplinary guideline-based stepped-care strategy (SCS) with recommendations regarding the appropriate non-surgical treatment modalities and optimal sequence for care has been developed. Implementation of this SCS in the general practice may be hampered by the negative attitude of general practitioners (GPs) towards the strategy. In order to develop a tailored implementation plan, we assessed the GPs' views regarding specific recommendations in the SCS and their working procedures with regard to OA. Methods. A survey was conducted among a random sample of Dutch GPs. Questions included the GP's demographical characteristics and the practice setting as well as how the management of OA was organized and whether the GPs supported the SCS recommendations. In particular, we assessed GP's views regarding the effectiveness of 14 recommended and non-recommended treatment modalities. Furthermore, we calculated their agreement with 7 statements based on the SCS recommendations regarding the sequence for care. With a linear regression model, we identified factors that seemed to influence the GPs' agreement with the SCS recommendations. Results: Four hundred fifty-six GPs (37%) aged 30-65 years, of whom 278 males (61%), responded. Seven of the 11 recommended modalities (i.e. oral Non-Steroidal Anti-Inflammatory Drugs, physical therapy, glucocorticoid intra-articular injections, education, lifestyle advice, acetaminophen, and tramadol) were considered effective by the majority of the GPs (varying between 95-60%). The mean agreement score, based on a 5-point scale, with the recommendations regarding the sequence for care was 2.8 (SD = 0.5). Ten percent of the variance in GPs' agreement could be explained by the GPs' attitudes regarding the effectiveness of the recommended and non-recommended non-surgical treatment modalities and the type of practice. Conclusion: In general, GPs support the recommendations in the SCS. Therefore, we expect that their attitudes will not impede a successful implementation in general practice. Our results provide sev

    Functional Swallowing Units (FSUs) as organs-at-risk for radiotherapy. PART 2:Advanced delineation guidelines for FSUs

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    Background and purpose: In a separate article (PART 1), a rationale and explanation of the physiology-and-anatomy-based concept of Functional Swallowing Units (FSUs) was presented. FSUs are swallowing muscles not included in the set of commonly defined swallowing organs at risk (SWOARs). They are involved in three crucial swallowing components: hyolaryngeal elevation (HLE), tongue base retraction (TBR) and tongue motion. This paper is a continuation of PART 1 and it provides detailed computed tomography (CT)-based delineation guidelines for FSUs, which presumably are also at risk of radiationinduced dysphagia. Material and methods: Following analysis of swallowing physiology and human anatomy, presented in PART 1, CT-based delineation guidelines for defined FSUs were created. Delineation was performed by the first author and revised by a panel of experts. Results and conclusions: Detailed delineation guidelines are presented for seven FSUs involved in HLE, TBR and tongue motion. The guidelines are supplemented by CT and MRI-based exemplary illustrations and complete CT/MRI-based delineation atlases (available online). This paper provides information essential to the implementation of the FSU concept in radiation practice, and supports uniform contouring, data collection and further improvement of swallowing sparing radiation-based strategies. (C) 2018 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults.

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    CONTEXT With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism. DESIGN Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial). SETTING Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSIONS Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment

    Enhanced CD1d phosphatidylserine presentation using a single-domain antibody promotes immunomodulatory CD1d-TIM-3 interactions

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    Background: CD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T-cell subsets and can be expressed by various malignancies. Antibody-mediated targeting of CD1d on multiple myeloma cells was reported to induce apoptosis and could therefore constitute a novel therapeutic approach. Methods: To determine how a CD1d-specific single-domain antibody (VHH) enhances binding of the early apoptosis marker annexin V to CD1d+ tumor cells we use in vitro cell-based assays and CRISPR-Cas9-mediated gene editing, and to determine the structure of the VHH1D17-CD1d(endogenous lipid) complex we use X-ray crystallography. Results: Anti-CD1d VHH1D17 strongly enhances annexin V binding to CD1d+ tumor cells but this does not reflect induction of apoptosis. Instead, we show that VHH1D17 enhances presentation of phosphatidylserine (PS) in CD1d and that this is saposin dependent. The crystal structure of the VHH1D17-CD1d(endogenous lipid) complex demonstrates that VHH1D17 binds the A′-pocket of CD1d, leaving the lipid headgroup solvent exposed, and has an electro-negatively charged patch which could be involved in the enhanced PS presentation by CD1d. Presentation of PS in CD1d does not trigger phagocytosis but leads to greatly enhanced binding of T-cell immunoglobulin and mucin domain containing molecules (TIM)-1 to TIM-3, TIM-4 and induces TIM-3 signaling. Conclusion: Our findings reveal the existence of an immune modulatory CD1d(PS)-TIM axis with potentially unexpected implications for immune regulation in both physiological and pathological conditions

    (R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

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    <p>Abstract</p> <p>Background</p> <p>Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate.</p> <p>Methods</p> <p><it>(R)</it>-[<sup>11</sup>C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on <it>(R)</it>-[<sup>11</sup>C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. <it>(R)</it>-[<sup>11</sup>C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM).</p> <p>Results</p> <p>All data analysis approaches indicated only modest differences in brain distribution of <it>(R)</it>-[<sup>11</sup>C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats.</p> <p>Conclusions</p> <p>P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.</p
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