Performance Analysis of Protocol Independent Multicasting-Dense Mode in Low Earth Orbit Satellite Networks

This research explored the implementation of Protocol Independent Multicasting - Dense Mode (PIM-DM) in a LEO satellite constellation. PIM-DM is a terrestrial protocol for distributing traffic efficiently between subscriber nodes by combining data streams into a tree-based structure, spreading from the root of the tree to the branches. Using this structure, a minimum number of connections are required to transfer data, decreasing the load on intermediate satellite routers. The PIM-DM protocol was developed for terrestrial systems and this research implemented an adaptation of this protocol in a satellite system. This research examined the PIM-DM performance characteristics which were compared to earlier work for On- Demand Multicast Routing Protocol (ODMRP) and Distance Vector Multicasting Routing Protocol (DVMRP) - all in a LEO satellite network environment. Experimental results show that PIM-DM is extremely scalable and has equivalent performance across diverse workloads. Three performance metrics are used to determine protocol performance in the dynamic LEO satellite environment, including Data-to- Overhead ratio, Received-to-Sent ratio, and End-to-End Delay. The OPNET® simulations show that the PIM-DM Data-to-Overhead ratio is approximately 80% and the protocol reliability is extremely high, achieving a Receive-to-Sent ratio of 99.98% across all loading levels. Finally, the PIM-DM protocol introduces minimal delay, exhibiting an average End-to-End Delay of approximately 76 ms; this is well within the time necessary to support real-time communications. Though fundamental differences between the DVMRP, ODMRP, and PIM-DM implementations precluded a direct comparison for each experiment, by comparing average values, PIM-DM generally provides equivalent or better performance

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Expression and clinical significance of Wnt players and Survivin pituitary tumours

Deregulation of the Wnt pathway has been implicated in oncogenesis of numerous tissues including the pituitary gland. Immunohistochemical localization and quantification of β-catenin, Cyclin D1, c-MYC and Survivin expression in 47 pituitary adenomas (35 non-functioning, seven GH-secreting, three prolactinomas, two CTHsecreting tumour) and six normal controls was undertaken in this study and correlation of protein expression to patient and tumour characteristics analysed. β-catenin was strictly membrane-bound with no difference observed between normal and tumour tissue. In contrast, Cyclin D1 and c-MYC localization was nuclear and significantly higher in tumour versus normal tissue (p<0.05). c-MYC expression correlated negatively with age at diagnosis (p00.006, R0−0.395) while Cyclin D1 expression correlated positively with age (p00.036, R00.306) and was higher in males than in females (p00.036). c-MYC expression was significantly lower in patients with functional tumours requiring octreotide treatment and in patients with non-functioning tumours suffering from hypopituitarism. Survivin expression was extremely low in tumours and absent in normal controls. Involvement of the canonical Wnt pathway appears to be minimal, given the segregation of β-catenin to the membrane. Our data suggest that c-MYC may have an important role in early pituitary tumorigenesis while Cyclin D1 is likely to promote tumour growth at a later stage. We also report a novel gender difference in Cyclin D1 expression, the biological significance of which merits further analysis. The reported reduction of c-MYC in functional tumours subsequently treated with octreotide further supports a role of c-MYC in early tumorigenesis and not in recurrence. The decrease in c-MYC in patients with hypopituitarism provides the first in vivo evidence for hormonal regulation of c-MYC expression.peer-reviewe

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls