A systematic evaluation of network protection responses in future converter-dominated power systems

This paper illustrates how converter interfaces, used to connect renewable energy sources, HVDC links and infeeds to the power system, may bring significant changes to the behaviour of protection systems in the future. A converter model, capable of providing adjustable fault responses, is used to investigate the response of power system protection to a range of fault conditions. Different scenarios have been simulated by applying different types of faults at different location of the transmission system with a variety of different converter response types. A dynamic, verified, relay model and a hardware relay device have been injected with the simulated results to ascertain network protection performance

Fetal heart rate development during labour

Background Fresh stillbirths (FSB) and very early neonatal deaths (VEND) are important global challenges with 2.6 million deaths annually. The vast majority of these deaths occur in low- and low-middle income countries. Assessment of the fetal well-being during pregnancy, labour, and birth is normally conducted by monitoring the fetal heart rate (FHR). The heart rate of newborns is reported to increase shortly after birth, but a corresponding trend in how FHR changes just before birth for normal and adverse outcomes has not been studied. In this work, we utilise FHR measurements collected from 3711 labours from a low and low-middle income country to study how the FHR changes towards the end of the labour. The FHR development is also studied in groups defined by the neonatal well-being 24 h after birth. Methods A signal pre-processing method was applied to identify and remove time periods in the FHR signal where the signal is less trustworthy. We suggest an analysis framework to study the FHR development using the median FHR of all measured heart rates within a 10-min window. The FHR trend is found for labours with a normal outcome, neonates still admitted for observation and perinatal mortality, i.e. FSB and VEND. Finally, we study how the spread of the FHR changes over time during labour. ResultsWhen studying all labours, there is a drop in median FHR from 134 beats per minute (bpm) to 119 bpm the last 150 min before birth. The change in FHR was significant (p Conclusion A significant drop in FHR the last 150 min before birth is seen for all neonates with a normal outcome or still admitted to the NCU at 24 h after birth. The observed earlier and larger drop in the perinatal mortality group may indicate that they struggle to endure the physical strain of labour, and that an earlier intervention could potentially save lives. Due to the low amount of data in the perinatal mortality group, a larger dataset is required to validate the drop for this group

Sipuleucel-T Immune Parameters Correlate with Survival: an Analysis of the Randomized Phase 3 Clinical Trials in Men with Castration-Resistant Prostate Cancer

Purpose: Sipuleucel-T, the first FDA-approved autologous cellular immunotherapy for treatment of advanced prostate cancer, is manufactured by activating peripheral blood mononuclear cells, including antigen presenting cells (APCs), with a fusion protein containing prostatic acid phosphatase. Analysis of data from three phase 3 trials was performed to immunologically characterize this therapy during the course of the three doses, and to relate the immunological responses to overall survival (OS). Methods: Sipuleucel-T product characteristics [APC numbers, APC activation (CD54 upregulation), and total nucleated cell (TNC) numbers] were assessed in three randomized, controlled phase 3 studies (N = 737). Antigen-specific cellular and humoral responses were assessed in a subset of subjects. The relationships between these parameters and OS were assessed. Results: APC activation occurred in the first dose preparation [6.2-fold, (4.65, 7.70); median (25th, 75th percentile)] and increased in the second [10.6-fold (7.83, 13.65)] and third [10.5-fold (7.89, 13.65)] dose preparations. Cytokines and chemokines associated with activated APCs were produced during the manufacture of each dose; T-cell activation-associated cytokines were detected in the second and third dose preparations. Antigen-specific T cells were detectable after administration of the first sipuleucel-T dose. Cumulative APC activation, APC number, and TNC number correlated with OS (P < 0.05). Antigen-specific immune responses were observed in 78.8 % of monitored subjects and their presence correlated with OS (P = 0.003). Conclusion: Sipuleucel-T broadly engages the immune system by activating APCs ex vivo and inducing long-lived immune responses in vivo. These data indicate antigen-specific immune activation as a mechanism by which sipuleucel-T prolongs OS

The high affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 β-1,6-N-acetylglusaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas

<p>Abstract</p> <p>Background</p> <p>The metastasis of cancer cells and leukocyte extravasation into inflamed tissues share common features. Specialized carbohydrates modified with sialyl Lewis x (sLe^x) antigens on leukocyte membranes are ligands for selectin adhesion molecules on activated vascular endothelial cells at inflammatory sites. The activity of the enzyme core 2 β1,6 <it>N</it>-acetylglucosaminyltransferase (C2GnT1) in leukocytes greatly increases their ability to bind to endothelial selectins. C2GnT1 is essential for the synthesis of core 2-branched O-linked carbohydrates terminated with sLe^x(C2-O-sLe^x). Our goal was to determine the expression profiles of C2-O-sLe^xin the malignant progression and metastasis of colorectal adenocarcinomas. The well characterized CHO-131 monoclonal antibody (mAb) specifically recognizes C2-O-sLe^xpresent in human leukocytes and carcinoma cells. Using CHO-131 mAb, we investigated whether C2-O-sLe^xwas present in 113 human primary colorectal adenocarcinomas, 10 colorectal adenomas, 46 metastatic liver tumors, 28 normal colorectal tissues, and 5 normal liver tissues by immunohistochemistry. We also examined mRNA levels of the enzyme core 2 β1,6-<it>N</it>-acetylglucosaminyltransferase (C2GnT1) in 20 well, 15 moderately, and 2 poorly differentiated colorectal adenocarcinomas, and in 5 normal colorectal tissues by using quantitative real-time polymerase chain reactions (RT-PCR).</p> <p>Results</p> <p>We observed high reactivity with CHO-131 mAb in approximately 70% of colorectal carcinomas and 87% of metastatic liver tumors but a lack of reactivity in colorectal adenomas and normal colonic and liver tissues. Positive reactivity with CHO-131 mAb was very prominent in neoplastic colorectal glands of well to moderately differentiated adenocarcinomas. The most intense staining with CHO-131 mAb was observed at the advancing edge of tumors with the deepest invasive components.</p> <p>Finally, we analyzed C2GnT1 mRNA levels in 37 colorectal adenocarcinomas and 5 normal colorectal tissues by RT-PCR. Significantly, we observed a greater than 15-fold increase in C2GnT1 mRNA levels in colorectal adenocarcinomas compared to normal colorectal tissues.</p> <p>Conclusion</p> <p>C2-O-sLe^x, detected by the CHO-131 mAb, is a tumor associated antigen whose expression is highly upregulated in colorectal adenocarcinomas and metastatic liver tumors compared to normal tissues. C2-O-sLe^xis a potentially useful early predictor of metastasis.</p