The technique of sensibility analysis studies the behavior of the ratio between the variation of output results and the variation of input parameters in general. This study performed in the reactor ...pressurizer, which is a component responsible for controlling of the pressure inside the vessel, has the fundamental importance in designing the security of any concept of an advanced reactor. In fact, for its feature of passive action of the pressurizer (there is no spray), this analysis becomes a necessary step for safety and performance of the plant. The direct method through code MODPRESS, which represents the pressurizer model of the International Reactor Innovative and Secure (IRIS), has required a huge computational effort. To solve this problem, artificial neural networks (ANNs), beyond faster, has been used to replace the MODPRESS in this article. The ANNs do not require linear behavior of the system and can use both, simulated or experimental data for their training and learning. In order this, we adopted a classical non-supervised training ANN for mapping and forecasting of the pressurized using initially simulated data. In next future, we will incorporate the experimental data from the operation of the CRCN-NE reduced-scale test facility mapping. Moreover, based on the results obtained in this study, one can conclude that the artificial neural networks are presented as an alternative to MODPRESS code, and artificial neural networks are actually a great tool to calculate the sensitivity coefficient.
•This article presents a sensibility analysis applied to Innovative Nuclear Reactor Concept.•This study has the fundamental importance in designing of any concept of an advanced compact reactor.•Artificial neural network has been used to simulate IRIS Reactor Pressurizer behavior.
To describe the effects on cerebral blood flow velocity (CBFV) of intermittent opening of the venoarterial bridge (VA bridge) during venoarterial extracorporeal membrane oxygenation (VA-ECMO).
...Prospective study in 22 newborns during VA ECMO. CBFV was measured in the pericallosal artery by Doppler ultrasound. Changes in peak systolic flow velocity (PSV), end diastolic flow velocity (EDV) and time-averaged mean flow velocity (TAM) on day 1, 2, 3, and 5 and at low ECMO flow (50- 150 ml/min) were analyzed (mean percentage+/-standard deviation (t-tests, p<0.05)). Changes >25% were considered relevant. The relationship between changes in CBFV and ECMO flow rate (Pearson correlation, p<0.01) was studied.
Opening of the VA bridge resulted in statistically significant and relevant decreases in PSV (35 +/- 18%), EDV (93 +/- 15%) and TAM (68 +/- 13%), persisting during the consecutive days of treatment. Smaller changes in CBFV at low ECMO flow were statistically significant and mostly relevant: PSV (15 +/- 7%), EDV (76 +/- 21%) and TAM (40 +/- 12%). Changes in CBFV were positively correlated to the ECMO flow.
Use of the VA bridge results in significant and relevant ECMO flow-dependent changes in CBFV, persisting during the treatment. The VA bridge should be used in such a way as to allow regular unclamping to be omitted.
Abstract
Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation
ERA CVD
Aims
Aging is associated with changes in the composition and function of ...the immune system, such as decreased B cell numbers and reduced antibody responses (1). In addition, aging is related to an increased incidence of inflammatory diseases, such as the lipid-driven chronic inflammatory disease atherosclerosis, the main underlying cause of cardiovascular disease (2). B cells play a major role in atherosclerosis progression by antibody secretion, antigen presentation and T cell regulation. Different B cell subsets, with either proatherogenic or antiatherogenic properties, have been identified in atherosclerosis, but the impact of aging on B cells during atherosclerosis remains to be elucidated. In contrast to young atherosclerotic mice where few B cells are found within the plaque, single cell RNA sequencing and flow cytometry data from our group revealed that B cells are one of the most dominant leukocytes present in atherosclerotic aortas from naturally aged LDLr-/- mice. In this study, we aimed to gain further insights into the role of these aged B cells on T cell immunity in atherosclerosis by depleting B cells in aged atherosclerotic mice.
Methods and Results
Aged (85-95 weeks) atherosclerotic male LDLr-/- mice were kept on a chow diet for six weeks, during which the mice received 250 µg B cell-depleting anti-CD20 antibody (Genentech) (n=12) or 250 µg rat IgG2a isotype control (n=12) once a week intraperitoneally. Mice that received the anti-CD20 antibody showed effective B cell depletion in the blood and lymphoid organs, such as the spleen and lymph nodes, but also locally in the atherosclerotic plaque. In addition, B cell depleted mice showed a significant increase in the percentage of T-bet expressing CD4+ T cells in aortic plaques compared to control mice (αCD20: 25.05±2.88% vs. ctrl: 15.94±2.14%, p<0.05). Furthermore, the percentage of RORyt+ and IL-17+ CD4+ T cells in the spleen and heart draining lymph nodes was increased after B cell depletion, indicating a shift towards Th17 differentiation.
Conclusions
Collectively, we show that CD20+ B cell depletion in aged LDLr-/- mice skews CD4+ T cells towards a Th1 phenotype in the atherosclerotic plaque and towards a Th17 phenotype in lymphoid organs, suggesting a protective role for aged B cells in atherosclerosis. However, B cells are a heterogeneous population and further research should elucidate whether aged B cells exert a pro- or anti-atherogenic role. In conclusion, our results indicate that aged B cells have an important function in CD4+ T cell differentiation and could be attractive targets to combat age-related cardiovascular disease.
Objective
To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre‐eclampsia before 26 weeks of gestation.
Design
Nationwide case series.
Setting
All ...Dutch tertiary perinatal care centres.
Population
All women diagnosed with severe pre‐eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014.
Methods
Women were identified through computerised hospital databases. Data were collected from medical records.
Main outcome measures
Maternal complications HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death, neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre‐eclampsia, premature delivery, and neonatal survival).
Results
We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0–25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre‐eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days.
Conclusions
Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling.
Tweetable
Severe early onset pre‐eclampsia comes with high maternal complication rates and poor neonatal survival.
Tweetable
Severe early onset pre‐eclampsia comes with high maternal complication rates and poor neonatal survival.
B and T cells are interconnected in the T follicular helper-germinal center B cell (T
-GC B cell) axis, which is hyperactive during atherosclerosis development and loss of control along this axis ...results in exacerbated atherosclerosis. Inhibition of the T
-GC B cell axis can be achieved by providing negative co-stimulation to T
cells through the PD-1/PD-L1 pathway. Therefore, we investigated a novel therapeutic strategy using PD-L1-expressing B cells to inhibit atherosclerosis. We found that IFNγ-stimulated B cells significantly enhanced PD-L1 expression and limited T
cell development. To determine whether IFNγ-B cells can reduce collar-induced atherosclerosis,
mice fed a Western-type diet were treated with PBS, B cells or IFNγ-B cells for a total of 5 weeks following collar placement. IFNγ-B cells significantly increased PD-L1
GC B cells and reduced plasmablasts. Interestingly, IFNγ-B cells-treated mice show increased atheroprotective Tregs and T cell-derived IL-10. In line with these findings, we observed a significant reduction in total lesion volume in carotid arteries of IFNγ-B cells-treated mice compared to PBS-treated mice and a similar trend was observed compared to B cell-treated mice. In conclusion, our data show that IFNγ-stimulated B cells strongly upregulate PD-L1, inhibit T
cell responses and protect against atherosclerosis.
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