Pro-inflammatory and anti-inflammatory cytokines are important mediators in the host response to infection. In contrast to the pro-inflammatory cytokines little is known about anti-inflammatory cytokines in community-acquired pneumonia (CAP) and their relation to disease severity.Circulating levels of three pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α) and two anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist (IL-1ra)) were measured using an enzyme immunoassay on admission, day 3 and day 5 in 24 patients with CAP. The modified British Thoracic Society (BTS) prognostic rule and Acute Physiology and Chronic Health Evaluation (APACHE) II score were used to assess disease severity.IL-6, TNF-α, IL-10 and IL-1ra concentrations were detected in most patients on admission and decreased significantly on day 3 and day 5 in all survivors. A significant difference between the BTS high-risk and low-risk groups was only found for IL-6 (median (range) 477 pg·mL−1(7.6–1402 pg·mL−1)versus81.6 pg·mL−1(0–943 pg·mL−1); p<0.05). IL-6 also correlated with the APACHE II scores on admission.Concentrations of anti-inflammatory cytokines were elevated on admission in community-acquired pneumonia but they did not correlate with disease severity scores.
Digital preservation aims to keep digital objects accessible over long periods of time, ensuring the authenticity and integrity of these digital objects. In such complex environments, Risk Management is a key factor in assuring the normal behaviour of systems over time. Currently, the digital preservation arena commonly uses Risk Management concepts to assess repositories. In this paper, we intend to go further and propose a perspective where Risk Management can be used not only to assess existing solutions, but also to conceive digital preservation environments. Thus, we propose a Risk Management-based approach to design and assess digital preservation environments, including:• the definition of context and identification of strategic objectives to determine specific requirements and characterize which consequences are acceptable within the identified context;• the identification, analysis and evaluation of threats and vulnerabilities that may affect the normal behaviour of a specific business or the achievement of the goals and conformance to the requirements identified in the context characterization; and, • definition of actions to deal with the risks associated with the identified threats and vulnerabilities.We generalize and survey the main requirements, threats, vulnerabilities and techniques that can be applied in the scope of digital preservation.
Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e−4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registration: NCT04370808.
Abstract-Enterprise Architecture approaches are used to provide rigorous descriptions of the organization-wide environment, manage the alignment of deployed services to the organization's mission, end ensure a clear separation of the concerns addressed in an architecture. Thus, an effective Enterprise Architecture approach assists in the management of relations and dependencies of any components of the organization environment and supports the integration and evolution of the architecture. However, the quality of that approach is strongly influenced by the precision of the architecture context description, a fact which is not always recognized.This paper focuses on the architecture context description and addresses the gap between the stakeholders' concerns and the resulting architecture. Based on a combination of established references and standards, we show how an explicit integration of the architecture context into the architecture model improves the linking of concerns and key elements of the architecture vision.We apply our approach to a subject of increasing concern in the Information Systems area: longevity of information. Digital preservation is an interdisciplinary problem, but existent initiatives address it in a very domain-centric way, making it impossible to integrate documented knowledge into an overall organization architecture. We analyze several references and models and derive a description of the architecture context and a capability model that supports incremental development through an explicit distinction between systems and their capabilities.The presented approach allows not just any organization to assess their current digital preservation awareness and evolve their architectures to address this challenge, but in particular demonstrates the added value of an explicit architecture context model in an Enterprise Architecture approach.
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