183 research outputs found

    Towards improving adaptability of capability driven development methodology in complex environment

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    We are triggered to incorporate adaptability in information system designs and methodologies corresponding to complex and unpredictable environment of today and tomorrow and to complex adaptive systems they are aimed for. Adaptability as non-functional requirement is being portrayed and investigated from broad multidisciplinary perspective that influences how dynamic business-IT alignment can be accomplished. Capability Driven Development methodology has supported delivering dynamic capabilities by providing context-aware self-adaptive platform in the CaaS project implementations, as our case study. Along with the already incorporated mechanisms, components that enable adaptability, there is open space for further evolutionary and deliberate change towards becoming truly appropriate methodology for dynamic reconfigurations of capabilities in organizations and business ecosystems that operate in complexity and uncertainty. The analysis and evaluation of adaptability of the CDD methodology through three dimensions (complexity of the external and internal environment, managerial profiling and artifact-integrated components) in this paper conclude with instigation of starting points towards achieving higher adaptability for complexity of the CDD methodology

    Alzheimer's Disease: a Review of its Visual System Neuropathology. Optical Coherence Tomography-a Potential Role As a Study Tool in Vivo

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    Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on in-vivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology.info:eu-repo/semantics/publishedVersio

    The Prevalence of the Genetic Polymorphism of GSTM1, GSTT1 and GSTP1 and Its Relationship with Clinical Criteria of Multiple Sclerosis (MS) Patients in Tehran

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    BACKGROUND AND OBJECTIVE: Multiple Sclerosis is the chronic inflammation of central nervous system with demyelinated lesions in the brain and spinal cord. The genetic polymorphisms associated with glutathione S-transferase enzymes involved in antioxidant defense in Iranian patients have not been investigated. Therefore, in the present study, the prevalence of the genetic polymorphism of glutathione S-transferase M1, P1 and T1 and its relationship with clinical criteria of MS patients with has been examined. METHODS: In this case-control study, 69 patients who referred to Sina Hospital in Tehran and had no panic attack within the last three months and 74 healthy subjects were interviewed. After examination by neurologist and blood sampling, DNA extraction was performed using Roche kit. Then, the genotypic variations of the samples were evaluated using RFLP-PCR and its prevalence was analyzed in relation with age, birth weight, malignancy (EDSS) and gender using GraphPad Prism software. FINDINGS: Most malignancies were observed in men (3.1±5.9) and the highest incidence rate was observed in those born in May (30%). Although the results of genotyping between the studied groups and their gender did not show any significant difference (OR: 2-4, p>0.05), patients with GSTM1 deficiency developed the disease at a lower age (32.8±2.6 years) compared with other patients (29.5±8.9 years) (CI-95%: 20.3–26.4, p=0.009). In addition, people with a rare GSTM1 allele who smoked cigarette had higher EDSS (CI-95%: 2.1–3.7, p=0.03). CONCLUSION: Based on the results of this study, the effect of GSTM1 on malignancy is indicative of its role in detoxification of tobacco products and can be used as an agent for early diagnosis of disease in people who are susceptible to this disease

    Optic Nerve Head Change in Non-Arteritic Anterior Ischemic Optic Neuropathy and Its Influence on Visual Outcome

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    To evaluate changes in cup/disc (C/D) diameter ratios and parapapillary atrophy in patients with non-arteritic anterior ischemic optic neuropathy (NA-AION), using morphometric methods.The clinical non-interventional study included 157 patients with unilateral or bilateral NA-AION. Optic disc photographs taken from both eyes at the end of follow-up were morphometrically examined.Follow-up was 86.3±70.3 months. Horizontal and vertical disc diameters (P = 0.30;P = 0.61, respectively), horizontal and vertical C/D ratios (P = 0.47;P = 0.19,resp.), and size of alpha zone and beta zone of parapapillary atrophy (P = 0.27;P = 0.32,resp.) did not differ significantly between affected eyes and contralateral normal eyes in patients with unilateral NA-AION. Similarly, horizontal and vertical disc diameters, horizontal and vertical C/D ratios, and size of alpha zone and beta zone did not vary significantly (all P>0.05) between the unaffected eyes of patients with unilateral NA-AION and the eyes of patients with bilateral NA-AION. Optic disc diameters, C/D ratios, size of alpha zone or beta zone of parapapillary atrophy were not significantly associated with final visual outcome in the eyes affected with NA-AION (all P>0.20) nor with the difference in final visual acuity between affected eyes and unaffected eyes in patients with unilateral NA-AION (all P>0.25).NA-AION did not affect C/D ratios nor alpha zone and beta zone of parapapillary atrophy. Optic disc size was not related to the final visual acuity outcome in NA-AION

    Recipient and donor thrombophilia and the risk of portal venous thrombosis and hepatic artery thrombosis in liver recipients

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    <p>Abstract</p> <p>Background</p> <p>Vascular complications, such as HAT, are an important cause of graft loss and recipient mortality. We aimed to characterize post-transplant thrombotic events in a cohort of liver transplant recipients, and identify independent risk factors for these complications.</p> <p>Methods</p> <p>We conducted a thrombophilic study of 293 orthotopic liver transplants performed in the Digestive Surgery Department of the 12 de Octubre Hospital (Madrid, Spain) between January 2001 and December 2006.</p> <p>Results</p> <p>The most frequent post-transplant thrombotic events were HAT (9%) and PVT (1.7%). The one variable associated with post-transplant thrombotic event was a high fibrinogen level in the global cohort of liver transplantation. But toxicity as event post-OLT has been associated with post-transplant thrombotic event in the retrospective group and high fibrinogen level and low protein C levels were associated post-transplant thrombotic event in the prospective group. Liver disease relapse (HR 6.609, p < 0.001), high levels of FVIII (HR 1.008, p = 0.019)) and low levels of antithrombin (HR 0.946, p < 0.001) were associated with poor overall survival (OS).</p> <p>In conclusion, high fibrinogen and decreased protein C levels were associated with allograft thrombosis. Further studies are required in order to assess the clinical relevance of these parameters in prospective studies and to study the effect of anticoagulation prophylaxis in this group of risk.</p

    Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma

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    The Asp358Ala variant in the interleukin-6 receptor (IL-6R) gene has been implicated in asthma, autoimmune and cardiovascular disorders, but its role in other respiratory conditions such as chronic obstructive pulmonary disease (COPD) has not been investigated. The aims of this study were to evaluate whether there is an association between Asp358Ala and COPD or asthma risk, and to explore the role of the Asp358Ala variant in sIL-6R shedding from neutrophils and its pro-inflammatory effects in the lung. We undertook logistic regression using data from the UK Biobank and the ECLIPSE COPD cohort. Results were meta-analyzed with summary data from a further three COPD cohorts (7,519 total cases and 35,653 total controls), showing no association between Asp358Ala and COPD (OR = 1.02 [95% CI: 0.96, 1.07]). Data from the UK Biobank showed a positive association between the Asp358Ala variant and atopic asthma (OR = 1.07 [1.01, 1.13]). In a series of in vitro studies using blood samples from 37 participants, we found that shedding of sIL-6R from neutrophils was greater in carriers of the Asp358Ala minor allele than in non-carriers. Human pulmonary artery endothelial cells cultured with serum from homozygous carriers showed an increase in MCP-1 release in carriers of the minor allele, with the difference eliminated upon addition of tocilizumab. In conclusion, there is evidence that neutrophils may be an important source of sIL-6R in the lungs, and the Asp358Ala variant may have pro-inflammatory effects in lung cells. However, we were unable to identify evidence for an association between Asp358Ala and COPD.This work was supported by the UK Medical Research Council [MR/L003120/1 and MR/J00345X/1]; the British Heart Foundation [RG/13/13/30194]; the UK National Institute for Health Research Cambridge Biomedical Research Centre; and the Cambridge NIHR BRC Cell Phenotyping Hub. The Cardiovascular Epidemiology Unit at the University of Cambridge is supported by the UK Medical Research Council [G0800270]; the British Heart Foundation [SP/09/002]; and the UK National Institute for Health Research Cambridge Biomedical Research Centre. The ECLIPSE study is supported by GlaxoSmithKline [SCO104960]. The COPDGene study was supported by National Institutes of Health [R01 HL089897 and R01 HL089856]. The Norway GenKOLS study is supported by GlaxoSmithKline [RES11080]. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA. Funding to pay the Open Access publication charges for this article was provided by University of Cambridge block grants from the Research Councils UK and the Charity Open Access Fund

    Requirements Engineering for Cyber Physical Production Systems

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    Traditional manufacturing and production systems are in the throes of a digital transformation. By blending the real and virtual production worlds, it is now possible to connect all parts of the production process: devices, products, processes, systems and people, in an informational ecosystem. This pa-per examines the underpinning issues that characterise the challenges for transforming traditional manufacturing to a Cyber Physical Production Sys-tem. Such a transformation constitutes a major endeavour for requirements engineers who need to identify, specify and analyse the effects that a multi-tude of assets need to be transformed towards a network of collaborating de-vices, information sources, and human actors. The paper reports on the e-CORE approach which is a systematic, analytical and traceable approach to Requirements Engineering and demonstrates its utility using an industrial-size application. It also considers the effect of Cyber Physical Production Systems on future approaches to requirements in dealing with the dynamic nature of such systems

    Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma

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    The Asp358Ala variant in the interleukin-6 receptor (IL-6R) gene has been implicated in asthma, autoimmune and cardiovascular disorders, but its role in other respiratory conditions such as chronic obstructive pulmonary disease (COPD) has not been investigated. The aims of this study were to evaluate whether there is an association between Asp358Ala and COPD or asthma risk, and to explore the role of the Asp358Ala variant in sIL-6R shedding from neutrophils and its pro-inflammatory effects in the lung. We undertook logistic regression using data from the UK Biobank and the ECLIPSE COPD cohort. Results were meta-analyzed with summary data from a further three COPD cohorts (7,519 total cases and 35,653 total controls), showing no association between Asp358Ala and COPD (OR = 1.02 [95% CI: 0.96, 1.07]). Data from the UK Biobank showed a positive association between the Asp358Ala variant and atopic asthma (OR = 1.07 [1.01, 1.13]). In a series of in vitro studies using blood samples from 37 participants, we found that shedding of sIL-6R from neutrophils was greater in carriers of the Asp358Ala minor allele than in non-carriers. Human pulmonary artery endothelial cells cultured with serum from homozygous carriers showed an increase in MCP-1 release in carriers of the minor allele, with the difference eliminated upon addition of tocilizumab. In conclusion, there is evidence that neutrophils may be an important source of sIL-6R in the lungs, and the Asp358Ala variant may have pro-inflammatory effects in lung cells. However, we were unable to identify evidence for an association between Asp358Ala and COPD.This work was supported by the UK Medical Research Council [MR/L003120/1 and MR/J00345X/1]; the British Heart Foundation [RG/13/13/30194]; the UK National Institute for Health Research Cambridge Biomedical Research Centre; and the Cambridge NIHR BRC Cell Phenotyping Hub. The Cardiovascular Epidemiology Unit at the University of Cambridge is supported by the UK Medical Research Council [G0800270]; the British Heart Foundation [SP/09/002]; and the UK National Institute for Health Research Cambridge Biomedical Research Centre. The ECLIPSE study is supported by GlaxoSmithKline [SCO104960]. The COPDGene study was supported by National Institutes of Health [R01 HL089897 and R01 HL089856]. The Norway GenKOLS study is supported by GlaxoSmithKline [RES11080]. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA. Funding to pay the Open Access publication charges for this article was provided by University of Cambridge block grants from the Research Councils UK and the Charity Open Access Fund

    Prevalence of Mistreatment or Belittlement among Medical Students – A Cross Sectional Survey at a Private Medical School in Karachi, Pakistan

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    Background: Mistreatment or belittlement of medical students either by faculty or fellow students has often been reported. Perception of mistreatment has also been associated with increased degree of psychological morbidity. There is a lack of such studies being conducted amongst the medical students of Pakistan. The aim of this study was to determine the prevalence and forms of perceived mistreatment and presence of mental health morbidity in a private medical school in Pakistan. Also, any association between mental health morbidity and mistreatment was to be identified. Methods: A cross sectional study was carried out on medical students from Aga Khan University Hospital, Karachi, Pakistan during the period of June-September 2007. A self administered questionnaire, adapted from Frank et al and Baldwin et al was distributed to a total of 350 students. The questionnaire consisted of three parts: the first dealing with the demographics of the population, the second concerning the various forms of mistreatment, while the third assessed the mental health of students using the General Health Questionnaire 12(GHQ12). Descriptive statistics were performed. The Chi-square test and Fisher\u27s exact tests were applied. Results: A total of 350 students were approached out of which 232 completed the questionnaire giving a response rate of 66.2%. Mistreatment was reported by 62.5% (145/232) of the respondents. Of these, 69.7% (83/145) were males and 54.9% (62/145) were females. There was a significant relationship between gender, year division, stress at medical school and possible use of drugs/alcohol and reported mistreatment but no statistical relationship was seen with psychiatric morbidity. The overall prevalence of psychological morbidity was 34.8% (77/221). Conclusion: This study suggests high prevalence of perceived mistreatment and psychological morbidity among Pakistani medical students. However, no association was found between these two aspects of medical student education. There is a need to bring about changes to make the medical education environment conducive to learning. Increased student feedback, support systems and guidance about progress throughout the year and the provision of adequate learning resources may provide help with resolving both of these issues
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