Benefits to the U.S. from Physicists Working at Accelerators Overseas

We illustrate benefits to the U.S. economy and technological infrastructure of U.S. participation in accelerators overseas. We discuss contributions to experimental hardware and analysis and to accelerator technology and components, and benefits stemming from the involvement of U.S. students and postdoctoral fellows in global scientific collaborations. Contributed to the proceedings of the Snowmass 2013 Community Summer Study.Comment: 23 pages, 1 figur

De novo mutations in histone modifying genes in congenital heart disease

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Patient Simulation: A Literary Synthesis of Assessment Tools in Anesthesiology

High-fidelity patient simulation (HFPS) has been hypothesized as a modality for assessing competency of knowledge and skill in patient simulation, but uniform methods for HFPS performance assessment (PA) have not yet been completely achieved. Anesthesiology as a field founded the HFPS discipline and also leads in its PA. This project reviews the types, quality, and designated purpose of HFPS PA tools in anesthesiology. We used the systematic review method and systematically reviewed anesthesiology literature referenced in PubMed to assess the quality and reliability of available PA tools in HFPS. Of 412 articles identified, 50 met our inclusion criteria. Seventy seven percent of studies have been published since 2000; more recent studies demonstrated higher quality. Investigators reported a variety of test construction and validation methods. The most commonly reported test construction methods included "modified Delphi Techniques" for item selection, reliability measurement using inter-rater agreement, and intra-class correlations between test items or subtests. Modern test theory, in particular generalizability theory, was used in nine (18%) of studies. Test score validity has been addressed in multiple investigations and shown a significant improvement in reporting accuracy. However the assessment of predicative has been low across the majority of studies. Usability and practicality of testing occasions and tools was only anecdotally reported. To more completely comply with the gold standards for PA design, both shared experience of experts and recognition of test construction standards, including reliability and validity measurements, instrument piloting, rater training, and explicit identification of the purpose and proposed use of the assessment tool, are required

Health State Utilities Associated with False-Positive Cancer Screening Results

Introduction: Early cancer detection can significantly improve patient outcomes and reduce mortality rates. Novel cancer screening approaches, including multi-cancer early detection tests, have been developed. Cost-utility analyses will be needed to examine their value, and these models require health state utilities. The purpose of this study was to estimate the disutility (i.e., decrease in health state utility) associated with false-positive cancer screening results.// Methods: In composite time trade-off interviews using a 1-year time horizon, UK general population participants valued 10 health state vignettes describing cancer screening with true-negative or false-positive results. Each false-positive vignette described a common diagnostic pathway following a false-positive result suggesting lung, colorectal, breast, or pancreatic cancer. Every pathway ended with a negative result (no cancer detected). The disutility of each false positive was calculated as the difference between the true-negative and each false-positive health state, and because of the 1-year time horizon, each disutility can be interpreted as a quality-adjusted life-year decrement associated with each type of false-positive experience.// Results: A total of 203 participants completed interviews (49.8% male; mean age = 42.0 years). The mean (SD) utility for the health state describing a true-negative result was 0.958 (0.065). Utilities for false-positive health states ranged from 0.847 (0.145) to 0.932 (0.059). Disutilities for false positives ranged from − 0.031 to − 0.111 (− 0.041 to − 0.111 for lung cancer; − 0.079 for colorectal cancer; − 0.031 to − 0.067 for breast cancer; − 0.048 to − 0.088 for pancreatic cancer).// Conclusion: All false-positive results were associated with a disutility. Greater disutility was associated with more invasive follow-up diagnostic procedures, longer duration of uncertainty regarding the eventual diagnosis, and perceived severity of the suspected cancer type. Utility values estimated in this study would be useful for economic modeling examining the value of cancer screening procedures