Категоріальна ситуація перфектності як засіб вираження відношень різночасності дій у рамках абзацу

Мета - довести, що категоріальна ситуація перфектності є основним із засобів вираження різночасності дій у тексті

Increasing cardio-thoracic productivity at Erasmus MC

The Thoraxcenter of Erasmus MC started an improvement project in 2015 in order to increase the number of open-heart surgeries by 150 for three consecutive years (450 in total, +46%), and to decrease the access time from 12–14 to 2–3 weeks by the end of 2016. This was required to attain economy of scale in a highly competitive market. In this paper we describe the first year of the project, focusing on its structure and interventions taken, resulting in 165 additional open-heart surgeries carried out in 2016 and a significantly shorter access time of 2–3 weeks

Chronic HIV infection induces transcriptional and functional reprogramming of innate immune cells

Chronic inflammation and immune dysfunction play a key role in the development of non-AIDS-related comorbidities. The aim of our study was to characterize the functional phenotype of immune cells in people living with HIV (PLHIV). We enrolled a cross-sectional cohort study of PLHIV on stable antiretroviral therapy and healthy controls. We assessed ex vivo cytokine production capacity and transcriptomics of monocytes and T cells upon bacterial, fungal, and viral stimulation. PLHIV exhibited an exacerbated proinflammatory profile in monocyte-derived cytokines, but not in lymphocyte-derived cytokines. Particularly, the production of the IL-1 beta to imiquimod, E. coli LPS, and Mycobacterium tuberculosis was increased, and this production correlated with plasma concentrations of high-sensitivity C-reactive protein and soluble CD14. This increase in monocyte responsiveness remained stable over time in subsequent blood sampling after more than 1 year. Transcriptome analyses confirmed priming of the monocyte IL-1 beta pathway, consistent with a monocyte-trained immunity phenotype. Increased plasma concentrations of beta-glucan, a well-known inducer of trained immunity, were associated with increased innate cytokine responses. Monocytes of PLHIV exhibited a sustained proinflammatory immune phenotype with priming of the IL-1 beta pathway. Training of the innate immune system in PLHIV likely plays a role in long-term HIV complications and provides a promising therapeutic target for inflammation-related comorbidities

Seasonal and Nonseasonal Longitudinal Variation of Immune Function

Different components of the immune response show large variability between individuals, but they also vary within the same individual because of host and environmental factors. In this study, we report an extensive analysis of the immune characteristics of 56 individuals over four timepoints in 1 single year as part of the Human Functional Genomics Project. We characterized 102 cell subsets using flow cytometry; quantified production of eight cytokines and two chemokines in response to 20 metabolic, bacterial, fungal, and viral stimuli; and measured circulating markers of inflammation. Taking advantage of the longitudinal sampling, both seasonal and nonseasonal sources of variability were studied. The circulating markers of inflammation IL-18, IL-18 binding protein, and resistin displayed clear seasonal variability, whereas the strongest effect was observed for alpha-1 antitrypsin. Cytokine production capacity also showed strong seasonal changes, especially after stimulation with the influenza virus, Borrelia burgdorferi, and Escherichia coli. Furthermore, we observed moderate seasonality effects on immune cell counts, especially in several CD4(+)/CD8(+) T cell subpopulations. Age of the volunteers was an important factor influencing IFN-gamma and IL-22 production, which matched the strong impact of age on several T cell subsets. Finally, on average, genetics accounted for almost 50% of the interindividual variance not already explained by age, sex, and body mass index, although this varies strongly for different parameters. In conclusion, seasonality is an important environmental factor that influences immune responses, in addition to specific genetic and nongenetic host factors, and this may well explain the seasonal variation in the incidence and severity of immune-mediated diseases

The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation

Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations in a cohort of 211 PLHIV on stable antiretroviral therapy and in 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist in T cell maturation and differentiation between PLHIV and HIV-uninfected controls: PLHIV had reduced percentages of CD4+ T cells and naïve T cells and increased percentages of CD8+ T cells, effector T cells, and T helper 17 (Th17) cells, together with increased Th17/regulatory T cell (Treg) ratios. PLHIV also exhibited altered B cell maturation with reduced percentages of memory B cells and increased numbers of plasmablasts. Determinants of the T and B cell composition in PLHIV included host factors (age, sex, and smoking), markers of the HIV reservoir, and CMV serostatus. Moreover, higher circulating Th17 percentages were associated with higher plasma concentrations of interleukin (IL) 6, soluble CD14, the gut homing chemokine CCL20, and intestinal fatty acid binding protein (IFABP). The changes in circulating lymphocytes translated into functional changes with reduced interferon (IFN)- γ responses of peripheral blood mononuclear cells to stimulation with Candida albicans and Mycobacterium tuberculosis. In conclusion, this comprehensive analysis confirms the importance of persistent abnormalities in the number and function of circulating immune cells in PLHIV on stable treatment.</jats:p

Sicherung von Dämmen, Deichen und Stauanlagen : Handbuch für Theorie und Praxis ; Vol. V - 2015

Die Universität Siegen beschäftigt sich seit über 15 Jahren wissenschaftlich und im Bereich der anwendungsorientierten Forschung mit diesem Thema und hat dazu mittlerweile fünf Symposien durchgeführt. Mit der Veröffentlichung soll die langjährige Tradition als etablierte wissenschaftliche Plattform mit einem Wissensaustausch auf europäischer Ebene fortgesetzt werden. Die Bearbeitung dieser Thematik erfolgt auf der Basis der bewährten Kooperation zwischen Geotechnik und Wasserbau an der Universität Siegen. Aktuelle Ereignisse, wie z.B. die aus England oder Australien im Februar des Jahres 2014, machen uns aber auch deutlich, dass ein absoluter Schutz gegen Extremereignisse nicht möglich ist. Sie zeigen aber auch, dass dort wo technischer Hochwasserschutz konsequent umgesetzt wurde Schäden vermieden werden konnten. Wir sind nach den Ereignissen in den vergangenen Jahren aufgefordert wissenschaftlich noch leistungsfähigere und duktilere Systeme zu entwickeln. Weiter ist die Wissenschaft in der Pflicht, die Zivile Sicherheit im Hochwasser-schutz permanent zu bewerten, zu bearbeiten und ganzheitliche-interdisziplinäre und länderübergreifende Lösungen für die Zivilgesellschaft einzufordern

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Increasing cardio-thoracic productivity at Erasmus MC

The Thoraxcenter of Erasmus MC started an improvement project in 2015 in order to increasethe number of open-heart surgeries by 150 for three consecutive years (450 in total, +46%), and to decrease the access time from 12–14 to 2–3 weeks by the end of 2016. This was required to attain economy of scale in a highly competitive market. In this paper we describe the first year of the project, focusing on its structure and interventions taken, resulting in 165 additional open-heart surgeries carried out in 2016 and a significantly shorter access time of 2–3 weeks