15 research outputs found
High-Volume Airborne Fluids Handling Technologies to Fight Wildfires
NASA recently partnered with the U.S. Forest Service (USFS) on a project to examine mission suitability and recommend policies and procedures for the use of very large aerial firefighting aircraft such as the Boeing 747 and DC-10 aerial retardant delivery aircraft. The aircraft under study included a 10Tanker DC-10 and an Evergreen B-747. NASA's Dryden Flight Research Center and Ames Research Center worked with the USFS to help determine the safe flight envelope for these Very Large Air Tanker (VLAT) aircraft for the USFS and the Department of the Interior (DOI). This new generation of supertankers includes aircraft like these that have as much as four times the delivery capacity of the previous generation of aerial firefighting aircraft. Dryden performed operational test and evaluation assessments and reported findings and recommendations on these aircraft in cooperation with Ames. The team developed, implemented, and directed an evaluation test plan for use in flight test and in simulation. Ames provided support using pilot-in-the-loop simulations and coordinated simulator models, flight profiles, and data analysis with Dryden. The test plan was designed to evaluate the suitability of VLAT aircraft as a function of mission environment. Based on this analysis, NASA generated interim flight envelope limitations to enhance safety and operational utility in the fire-retardant delivery mission. These recommended flight limitations were adopted by the USFS. The 10Tanker DC-10 has been in use for several years with the California Department of Forestry and Fire Protection(Cal-Fire), but until NASA took on the challenge of reviewing VLAT capabilities and limitations, the USFS was hesitant to add them to the federal wildfire arsenal. The DC-10 delivery system is based on an externally mounted set of tanks and a bomb-bay style set of clamshell doors that are opened in precisely calibrated ways to deliver the amounts and concentrations of retardant called for by the specific wildfire situation. The system was manufactured by Jordan Air of Central Point, OR, and was installed by Victorville Aerospace in Victorville, CA. It can deliver 12,000 gallons (45.4 kL) of retardant in as little as eight seconds. The aircraft can deliver a partial load of retardant and make multiple drops on the same flight, or the entire load can be rapidly delivered in one pass if required for maximum coverage. The Evergreen 747 uses internal tankage and a pressurized delivery system to enable volume and coverage levels that also meet USFS requirements, but enables computer control of flow for desired precision. This system was designed and built by Adaptive Aerospace of Tehachapi, CA and can deliver about 20,000 gallons (75.7 kL) of retardant in approximately ten seconds. The 747 can also make multiple independent drops, or deliver the entire load at once. NASA found that both of these VLAT aircraft are compatible with the wildfire suppression mission when used to supplement other aerial retardant delivery platforms. The major recommendations for deployment that resulted from this study relate to terrain clearance, the type of terrain in the drop area, availability of qualified lead planes to guide the VLAT approach to the drop area, and low-altitude maneuvering limitations. NASA s analysis suggests that with the appropriate flight procedures, these aircraft will provide a powerful set of tools to fight wildfires
HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer
BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse