The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Private versus Shared, Automated Electric Vehicles for U.S. Personal Mobility: Energy Use, Greenhouse Gas Emissions, Grid Integration, and Cost Impacts.

Transportation is the fastest-growing source of greenhouse gas (GHG) emissions and energy consumption globally. While the convergence of shared mobility, vehicle automation, and electrification has the potential to drastically reduce transportation impacts, it requires careful integration with rapidly evolving electricity systems. Here, we examine these interactions using a U.S.-wide simulation framework encompassing private electric vehicles (EVs), shared automated EVs (SAEVs), charging infrastructure, controlled EV charging, and a grid economic dispatch model to simulate personal mobility exclusively using EVs. We find that private EVs with uncontrolled charging would reduce GHG emissions by 46% compared to gasoline vehicles. Private EVs with fleetwide controlled charging would achieve a 49% reduction in emissions from baseline and reduce peak charging demand by 53% from the uncontrolled scenario. We also find that an SAEV fleet 9% the size of today's active vehicle fleet can satisfy trip demand with only 2.6 million chargers (0.2 per EV). Such an SAEV fleet would achieve a 70% reduction in GHG emissions at 41% of the lifecycle cost as a private EV fleet with controlled charging. The emissions and cost advantage of SAEVs is primarily due to reduced vehicle manufacturing compared with private EVs

Private versus Shared, Automated Electric Vehicles for U.S. Personal Mobility: Energy Use, Greenhouse Gas Emissions, Grid Integration, and Cost Impacts.

Transportation is the fastest-growing source of greenhouse gas (GHG) emissions and energy consumption globally. While the convergence of shared mobility, vehicle automation, and electrification has the potential to drastically reduce transportation impacts, it requires careful integration with rapidly evolving electricity systems. Here, we examine these interactions using a U.S.-wide simulation framework encompassing private electric vehicles (EVs), shared automated EVs (SAEVs), charging infrastructure, controlled EV charging, and a grid economic dispatch model to simulate personal mobility exclusively using EVs. We find that private EVs with uncontrolled charging would reduce GHG emissions by 46% compared to gasoline vehicles. Private EVs with fleetwide controlled charging would achieve a 49% reduction in emissions from baseline and reduce peak charging demand by 53% from the uncontrolled scenario. We also find that an SAEV fleet 9% the size of today's active vehicle fleet can satisfy trip demand with only 2.6 million chargers (0.2 per EV). Such an SAEV fleet would achieve a 70% reduction in GHG emissions at 41% of the lifecycle cost as a private EV fleet with controlled charging. The emissions and cost advantage of SAEVs is primarily due to reduced vehicle manufacturing compared with private EVs

Audio Cues and Its Application to Virtual Fence

Virtual fence has the possibility to improve management practices for grazing livestock. It will allow producers to utilize areas for grazing that are otherwise unusable due to the lack of fencing or ability to fence as well as make rotational grazing easier to manage. The virtual fence project I’m working on aims to make a product that is easily transportable, cost effective, and is successful for including and excluding animals in a certain area. This research focuses on the audio cue which is applied prior to an electrical stimulus in the hopes that the animal will be able to associate the sound with a shock and learn this as an avoidance cue. The specific aims are to determine: (1) Is sound an effective stimulus to include/exclude cattle from a motivated source; (2) Does the tone and duration of the sound change the effectiveness of the stimulus; (3) Does the direction/location of sound affect the reaction of associative learning in cattle. This research will help us better understand sound when used as an associated cue and will hopefully reduce the amount of times the animal is shocked and therefore increase the effectiveness of virtual fence

Results from a Theory-Guided Survey to Support Breast Cancer Trial Participation: Barriers, Enablers, and What to Do about them

Background: Ensuring adequate, informed, and timely participation in clinical trials is a multifactorial problem. We have previously developed a systematic, tailorable survey development approach that is informed by theory, can identify barriers and enablers to participation, and can suggest recruitment strategies to address these issues. In this study, we surveyed subscribers to the Canadian Breast Cancer Network (CBCN) in order to identify a comprehensive list of theory-informed barriers and enablers relevant to participation in a hypothetical breast cancer trial. Methods: We developed and conducted an online survey of breast cancer patients informed by the Theoretical Domains Framework and designed to determine previous experience with clinical trials, knowledge about clinical trials, and importance of a comprehensive list of barriers and enablers to trial participation. Participants were contacted by email or through social media. Results: From 2451 subscribers of the CBCN, we received 244 responses and 210 completed surveys (244/2451 or 9.9% participation, 210/244 or 86.1% completion). A total of 38% of respondents indicated experience in trial participation, but 83% indicated confidence in their knowledge about clinical trials. Those who had previously participated in clinical trials were more confident in their knowledge (χ2= 6.77, p = 0.009) and answered more knowledge questions (t = −3.90 p = 0.000). Endorsed barriers and enablers to participation included 39 factors across 12 of 14 domains relevant to behaviour change. Our approach identifies barriers that might be meaningfully addressed by careful knowledge provision (‘If I would learn more about my condition’; ‘If I find the trial documents hard to understand’), those that may require other theory-informed approaches to address (‘my feelings about the quality of my drug plan’; ‘my worry over unknown side effects’), and those that may require tailored approaches depending on participant differences such as previous experience in trials (‘If there were patient-friendly decision-making tools to help you make your participation decision’). Discussion: This work demonstrates that a comprehensive, theory-guided survey of barriers and enablers to participation in breast cancer clinical trials is feasible, can lead to detailed knowledge about the issues related to participation in specific trials, and most importantly, can lead to insights about evidence-based ways to better support patient participation

A multi-stakeholder approach in optimising patients' needs in the benefit assessment process of new metastatic breast cancer treatments.

There is a growing understanding as science evolves that different cancer types require different approaches to treatment evaluation, especially in the metastatic stages. The introduction of new metastatic breast cancer (MBC) treatments may be hindered by several elements, including the availability of relevant evidence related to disease-specific outcomes, the benefit assessment process around the evaluation of the clinical benefit and the patients' need of new treatments. The Steering Committee (SC) found that not all issues relevant to MBC patients are consistently considered in the current benefit assessment process of new treatments. Among these are overall survival, time-to-event endpoints (e.g. progression-free survival), patients' priorities, burden of disease, MBC-specific quality of life, value in delaying chemotherapy, route of administration, side effects and toxicities, treatment adherence and the benefit of real-world evidence. This paper calls on decision makers to (1) Include MBC-specific patient priorities and outcomes in the overall benefit assessments of new MBC treatments; (2) Enhance multi-stakeholder collaboration in order to improve MBC patient outcomes