Collision tumors revealed by prospectively assessing subtype-defining molecular alterations in 904 individual prostate cancer foci.

BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODSFrom the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTSBased on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSIONInterfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDINGEarly Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063)

The emergence of health inequalities in early adulthood: evidence on timing and mechanisms from a West of Scotland cohort

Background Evidence is inconsistent as to whether or not there are health inequalities in adolescence according to socio-economic position (SEP) and whether or when they emerge in early adulthood. Despite the large health inequalities literature, few studies have simultaneously compared the relative importance of ?health selection? versus ?social causation? at this life-stage. This study followed a cohort through the youth-adult transition to: (1) determine whether, and if so, when, health inequalities became evident according to both class of origin and current SEP; (2) compare the importance of health selection and social causation mechanisms; and (3) investigate whether these phenomena vary by gender. Methods Data are from a West-of-Scotland cohort, surveyed five times between age 15 (in 1987, N=1,515, response=85%) and 36. Self-reported physical and mental health were obtained at each survey. SEP was based on parental occupational class at 15, a combination of own education or occupational status at 18 and own occupational class (with an additional non-employment category) at older ages. In respect of when inequalities emerged, we used the relative index of inequality to examine associations between both parental and own current SEP and health at each age. In respect of mechanisms, path models, including SEP and health at each age, investigated both inter and intra-generational paths from SEP to health (?causation?) and from health to SEP (?selection?). Analyses were conducted separately for physical and mental health, and stratified by gender. Results Associations between both physical and mental health and parental SEP were non-significant at every age. Inequalities according to own SEP emerged for physical health at 24 and for mental health at 30. There was no evidence of selection based on physical health, but some evidence of associations between mental health in early adulthood and later SEP (intra-generational selection). Paths indicated intra-generational (males) and inter-generational (females) social causation of physical health inequalities, and intra-generational (males and females) and inter-generational (females) social causation of mental health inequalities. Conclusions The results suggest complex and reciprocal relationships between SEP and health and highlight adolescence and early adulthood as a sensitive period for this process, impacting on future life-chances and health

THE AMERICAN SOCIETY OFMECHANICAL ENGINEERS A Simple Model to Simulate Subsonic Intakes and Propelling Nozzles of Aircraft Gas Turbine Engines

ABSTRACT In this paper the subsonic intake and the propelling nozzle of aircraft gas turbine engines are modeled for the purpose of simulate. Each component is considered as a variable area duct which is divided into a number of elemental sections. Flow properties are calculated in a step by step manner in each section taking into account friction and area change. The underlying theory of the model and a brief description of the computer program are given. The program has been written in Fortran 77 and runs on IBM AT or 100% compatible micro computers

A design study of economically viable PEM fuel cell

This paper critically examines the conventional design of the low temperature (up to 80°C) Proton Exchange Membrane (PEM) fuel cell and a manufacturing design that does not depend on bi polar plates is presented. The fuel cell cost depends on the material and also on the complex manufacturing process. Materials that can be easily machined but still suitable in a fuel cell environment have been extensively researched and appropriately chosen. The design also incorporates greatly simplified manufacturing processes of the components. As a result the cost of the fuel cell can be driven down considerably. A series of tests were performed with a number of key operating parameters to provide vital performance data and to decide on the optimal operating conditions for the fuel cell. Comparisons were made with the published performance data of conventional PEM fuel cell to prove the design concept. It was observed that the proposed design performs comparatively better at higher current densities

Flexion-Induced Automatic Prosthetic for Partial-Finger Amputees

Partial hand amputations are the most common type of amputations, however the current prosthetic solutions are not always viable for most patients due to the high cost. This project aims to increase dexterity and range of motion to partial finger amputees at a greatly reduced cost by creating an articulating prosthetic using 3D printing technology. Two different design solutions were made in order to accomplish these goals: a simple mechanical finger and a robotic flexing finger, both of which achieve flexion via a pulley system emulating tendons in a natural finger. The prosthesis were tested for improvements in dexterity and range of motion using the Purdue Pegboard Test and a goniometer, respectively. The results of this project show that there are alternative, less expensive prosthetic options that still perform comparably to current products for partial finger amputees. Next steps for this project include further research into alternate materials and expanding the design for other types of partial hand amputations