2012 NASA Range Safety Annual Report

This report provides a NASA Range Safety (NRS) overview for current and potential range users. This report contains articles which cover a variety of subject areas, summaries of various NASA Range Safety Program (RSP) activities performed during the past year, links to past reports, and information on several projects that may have a profound impact on the way business will be conducted in the future. Specific topics discussed in the 2012 NASA Range Safety Annual Report include a program overview and 2012 highlights; Range Safety Training; Independent Assessments; Support to Program Operations at all ranges conducting NASA launch/flight operations; a continuing overview of emerging range safety-related technologies; and status reports from all of the NASA Centers that have Range Safety responsibilities

2010 NASA Range Safety Annual Report

this report provides a NASA Range Safety overview for current and potential range users. This report contains articles which cover a variety of subject areas, summaries of various NASA Range Safety Program activities conducted during the past year, links to past reports, and information on several projects that may have a profound impact on the way business will be done in the future. Specific topics discussed in the 2010 NASA Range Safety Annual Report include a program overview and 2010 highlights; Range Safety Training; Range Safety Policy revision; Independent Assessments; Support to Program Operations at all ranges conducting NASA launch/flight operations; a continuing overview of emerging range safety-related technologies; and status reports from all of the NASA Centers that have Range Safety responsibilities. Every effort has been made to include the most current information available. We recommend this report be used only for guidance and that the validity and accuracy of all articles be verified for updates. Once again, the web-based format was used to present the annual report

2011 NASA Range Safety Annual Report

Welcome to the 2011 edition of the NASA Range Safety Annual Report. Funded by NASA Headquarters, this report provides a NASA Range Safety overview for current and potential range users. As is typical with odd year editions, this is an abbreviated Range Safety Annual Report providing updates and links to full articles from the previous year's report. It also provides more complete articles covering new subject areas, summaries of various NASA Range Safety Program activities conducted during the past year, and information on several projects that may have a profound impact on the way business will be done in the future. Specific topics discussed and updated in the 2011 NASA Range Safety Annual Report include a program overview and 2011 highlights; Range Safety Training; Range Safety Policy revision; Independent Assessments; Support to Program Operations at all ranges conducting NASA launch/flight operations; a continuing overview of emerging range safety-related technologies; and status reports from all of the NASA Centers that have Range Safety responsibilities. Every effort has been made to include the most current information available. We recommend this report be used only for guidance and that the validity and accuracy of all articles be verified for updates. Once again the web-based format was used to present the annual report. We continually receive positive feedback on the web-based edition and hope you enjoy this year's product as well. As is the case each year, contributors to this report are too numerous to mention, but we thank individuals from the NASA Centers, the Department of Defense, and civilian organizations for their contributions. In conclusion, it has been a busy and productive year. I'd like to extend a personal Thank You to everyone who contributed to make this year a successful one, and I look forward to working with all of you in the upcoming year

NASA Range Safety Annual Report 2007

As always, Range Safety has been involved in a number of exciting and challenging activities and events. Throughout the year, we have strived to meet our goal of protecting the public, the workforce, and property during range operations. During the past year, Range Safety was involved in the development, implementation, and support of range safety policy. Range Safety training curriculum development was completed this year and several courses were presented. Tailoring exercises concerning the Constellation Program were undertaken with representatives from the Constellation Program, the 45th Space Wing, and the Launch Constellation Range Safety Panel. Range Safety actively supported the Range Commanders Council and it subgroups and remained involved in updating policy related to flight safety systems and flight safety analysis. In addition, Range Safety supported the Space Shuttle Range Safety Panel and addressed policy concerning unmanned aircraft systems. Launch operations at Kennedy Space Center, the Eastern and Western ranges, Dryden Flight Research Center, and Wallops Flight Facility were addressed. Range Safety was also involved in the evaluation of a number of research and development efforts, including the space-based range (formerly STARS), the autonomous flight safety system, the enhanced flight termination system, and the joint advanced range safety system. Flight safety system challenges were evaluated. Range Safety's role in the Space Florida Customer Assistance Service Program for the Eastern Range was covered along with our support for the Space Florida Educational Balloon Release Program. We hope you have found the web-based format both accessible and easy to use. Anyone having questions or wishing to have an article included in the 2008 Range Safety Annual Report should contact Alan Dumont, the NASA Range Safety Program Manager located at the Kennedy Space Center, or Michael Dook at NASA Headquarters

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(−07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10(−05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes