52 research outputs found

    Cost-based resilience assessment of bridges subjected to earthquakes

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    European Commission H2020-Marie Skłodowska-Curie Research Grants Scheme MSCA-IF-2016 (grant agreement No 746298: TRANSRISK – Vulnerability and risk assessment of transportation systems of assets exposed to geo-hazards)

    Osteosarcoma microenvironment: whole-slide imaging and optimized antigen detection overcome major limitations in immunohistochemical quantification.

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    BACKGROUND: In osteosarcoma survival rates could not be improved over the last 30 years. Novel biomarkers are warranted to allow risk stratification of patients for more individual treatment following initial diagnosis. Although previous studies of the tumor microenvironment have identified promising candidates, novel biomarkers have not been translated into routine histopathology. Substantial difficulties regarding immunohistochemical detection and quantification of antigens in decalcified and heterogeneous osteosarcoma might largely explain this translational short-coming. Furthermore, we hypothesized that conventional hot spot analysis is often not representative for the whole section when applied to heterogeneous tissues like osteosarcoma. We aimed to overcome these difficulties for major biomarkers of the immunovascular microenvironment. METHODS: Immunohistochemistry was systematically optimized for cell surface (CD31, CD8) and intracellular antigens (FOXP3) including evaluation of 200 different antigen retrieval conditions. Distribution patterns of these antigens were analyzed in formalin-fixed and paraffin-embedded samples from 120 high-grade central osteosarcoma biopsies and computer-assisted whole-slide analysis was compared with conventional quantification methods including hot spot analysis. RESULTS: More than 96% of osteosarcoma samples were positive for all antigens after optimization of immunohistochemistry. In contrast, standard immunohistochemistry retrieved false negative results in 35-65% of decalcified osteosarcoma specimens. Standard hot spot analysis was applicable for homogeneous distributed FOXP3+ and CD8+ cells. However, heterogeneous distribution of vascular CD31 did not allow reliable quantification with hot spot analysis in 85% of all samples. Computer-assisted whole-slide analysis of total CD31- immunoreactive area proved as the most appropriate quantification method. CONCLUSION: Standard staining and quantification procedures are not applicable in decalcified formalin-fixed and paraffin-embedded samples for major parameters of the immunovascular microenvironment in osteosarcoma. Whole-slide imaging and optimized antigen retrieval overcome these limitations

    The potential utility of B cell-directed biologic therapy in autoimmune diseases

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    Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs—rituximab, a chimeric monoclonal antibody against the B cell-specific surface marker CD20—was recently approved for treating rheumatoid arthritis in patients with an inadequate response to other biologic therapies. The aim of this review is to discuss the potential use of rituximab in the management of other autoimmune disorders. Results from early phase clinical trials indicate that rituximab may provide clinical benefit in systemic lupus erythematosus, Sjögren’s syndrome, vasculitis, and thrombocytopenic purpura. Numerous case reports and several small pilot studies have also been published reporting the use of rituximab in conditions such as myositis, antiphospholipid syndrome, Still’s disease, and multiple sclerosis. In general, the results from these preliminary studies encourage further testing of rituximab therapy in formalized clinical trials. Based on results published to date, it is concluded that rituximab, together with other B cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these difficult-to-treat autoimmune disorders

    Resilience of bridges subjected to earthquakes: A case study on a portfolio of road bridges

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    Transportation infrastructure resilience is of paramount importance for societies and economies, therefore its quantification is urgently needed. Infrastructure assets and networks should be robust, i.e. they should have the ability to absorb the actions of natural hazards with minimal loss of functionality and thus should be designed to have redundancy for providing alternatives for damaged components. In addition, resilience enhancement requires the availability of resources and prioritization of goals, for rapid restoration of the affected assets functionality at an acceptable level. Hence, owners and operators would be benefited in the decision-making process from quantifications of resilience that account for different seismic events, the type and extent of expected damage, and the time of restoration. This paper is an application that takes into account the abovementioned factors in the resilience assessment of representative bridges in Thessaloniki, Greece, exposed to earthquakes. In particular, this application quantifies the robustness of bridges against different seismic hazard scenarios, by utilizing realistic fragility curves and the rapidity of the recovery and/or retrofitting after the occurrence of a certain degree of damage, based on realistic restoration functions. Two different approaches for the modelling of the restoration tasks are examined. Resilience assessment is based on a well-informed resilience index, which is a function of the time-variant functionality of the infrastructure over the restoration time for these scenarios. The results of this research are expected to facilitate owners to enhance decision-making and risk management toward more resilient infrastructure

    Cost-based resilience assessment of bridges subjected to earthquakes

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    Purpose Transport infrastructure resilience is of paramount importance for societies, therefore its quantification is urgently needed. A resilience assessment framework based on well-informed resilience indices is presented and applied for assessing the resilience of representative bridges exposed to earthquakes. Design/methodology/approach The framework quantifies the robustness of bridges against different seismic hazard scenarios, by utilising realistic fragility functions and the rapidity of the recovery and/or retrofitting after the occurrence of a certain degree of damage, based on realistic restoration functions. Findings Two different approaches for the modelling of the restoration tasks are examined. Both direct losses due to structural damage and indirect losses due to traffic disruption are estimated. Originality/value A new cost-based resilience index is introduced and alternative approaches for expressing the restoration strategies are examined and assessed. The results facilitate owners to enhance cost-based resilience management toward more resilient infrastructure.</p

    Bone and joint infections

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    The European Society for Paediatric Infectious Diseases (ESPID) Bone and Joint Infection Guidelines (ESPID Guidelines) are intended for use by health providers who take care of children with bone and joint infection (BJI). Although BJI can include a diverse range of presentations, these guidelines will focus on “acute, hematogenous BJI in children,” with an emphasis on bacterial infections.ESPID Guidelines are consensus-based practice recommendations developed in a systematic manner that aim to be clear, valid and reliable, and presented with clinical applicability. Because evidence from large randomized controlled trials is rare or lacking, practice statements and recommendations provided here frequently reflect our expert consensus process based on best current practice.Although these guidelines include evidence-based and opinion-based recommendations for the diagnosis and management of children with BJI, these guidelines may not provide the best clinical solution and are not intended to serve as a substitute for the clinical judgment of physicians in individual cases or to establish a protocol valid for all children with these infections. Consequently, they do not represent the “only” appropriate approach for children with this kind of infection.We kindly refer to the full version available online (Supplemental Digital Content, http://links.lww.com/INF/C729) for more information on sources used, literature search strategies, guideline development methodology and the ESPID Review Team.The authors of these ESPID Guidelines have made considerable efforts to ensure that the information upon which they are based is accurate and up-to-date. Users of these guidelines are strongly recommended to confirm that the information contained within them, especially drug doses, is correct by way of independent sources. ESPID and the authors of these guidelines accept no responsibility for any inaccuracies, information perceived as misleading or the outcome of any treatment regimen detailed in the guidelines

    A national study of antibiotic use in Greek pediatric hematology oncology and bone marrow transplant units

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    Objective: We surveyed antimicrobials used in Greek pediatric hematology-oncology (PHO) and bone marrow transplant (BMT) units before and after an intervention involving education regarding the 2017 clinical practice guidelines (CPG) for the management of febrile neutropenia in children with cancer and hematopoietic stem-cell transplant recipients. Design: Antibiotic prescribing practices were prospectively recorded between June 2016 and November 2017. Intervention: In December 2017, baseline data feedback was provided, and CPG education was provided. Prescribing practices were followed for one more year. For antibiotic stewardship, days of therapy, and length of therapy were calculated. Setting: Five of the 6 PHO units in Greece and the single pediatric BMT unit participated. Participants: Admitted children in each unit who received the first 15 new antibiotic courses each month. Results: Administration of ≥4 antibiotics simultaneously and administration of antibiotics with overlapping activity for ≥2 days were significantly more common in PHO units in general hospitals compared to children&apos;s hospitals. Use of at least 1 antifungal was recorded in ∼47% of the patients before and after the intervention. De-escalation and/or discontinuation of antibiotics on day 6 of initial treatment increased significantly from 43% to 53.5% (P =.032). Although the number of patients requiring intensive care support for sepsis did not change, a significant drop was noted in all-cause mortality (P =.008). Conclusions: We recorded the antibiotic prescribing practices in Greek PHO and BMT units, we achieved improved prescribing with a simple intervention, and we identified areas in need of improvement. © The Author(s), 2022
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