Ultra-high resolution HLA genotyping and allele discovery by highly multiplexed cDNA amplicon pyrosequencing

Background: High-resolution HLA genotyping is a critical diagnostic and research assay. Current methods rarely achieve unambiguous high-resolution typing without making population-specific frequency inferences due to a lack of locus coverage and difficulty in exon-phase matching. Achieving high-resolution typing is also becoming more challenging with traditional methods as the database of known HLA alleles increases. Results: We designed a cDNA amplicon-based pyrosequencing method to capture 94% of the HLA class I open-reading-frame with only two amplicons per sample, and an analogous method for class II HLA genes, with a primary focus on sequencing the DRB loci. We present a novel Galaxy server-based analysis workflow for determining genotype. During assay validation, we performed two GS Junior sequencing runs to determine the accuracy of the HLA class I amplicons and DRB amplicon at different levels of multiplexing. When 116 amplicons were multiplexed, we unambiguously resolved 99%of class I alleles to four- or six-digit resolution, as well as 100% unambiguous DRB calls. The second experiment, with 271 multiplexed amplicons, missed some alleles, but generated high-resolution, concordant typing for 93% of class I alleles, and 96% for DRB1 alleles. In a third, preliminary experiment we attempted to sequence novel amplicons for other class II loci with mixed success. Conclusions: The presented assay is higher-throughput and higher-resolution than existing HLA genotyping methods, and suitable for allele discovery or large cohort sampling. The validated class I and DRB primers successfully generated unambiguously high-resolution genotypes, while further work is needed to validate additional class II genotyping amplicons

The T2K ND280 Off-Axis Pi-Zero Detector

The Pi-Zero detector (P{\O}D) is one of the subdetectors that makes up the off-axis near detector for the Tokai-to-Kamioka (T2K) long baseline neutrino experiment. The primary goal for the P{\O}D is to measure the relevant cross sections for neutrino interactions that generate pi-zero's, especially the cross section for neutral current pi-zero interactions, which are one of the dominant sources of background to the electron neutrino appearance signal in T2K. The P{\O}D is composed of layers of plastic scintillator alternating with water bags and brass sheets or lead sheets and is one of the first detectors to use Multi-Pixel Photon Counters (MPPCs) on a large scale.Comment: 17 pages, submitted to NIM

Are adolescents with high socioeconomic status more likely to engage in alcohol and illicit drug use in early adulthood?

<p>Abstract</p> <p>Background</p> <p>Previous literature has shown a divergence by age in the relationship between socioeconomic status (SES) and substance use: adolescents with low SES are more likely to engage in substance use, as are adults with high SES. However, there is growing evidence that adolescents with high SES are also at high risk for substance abuse. The objective of this study is to examine this relationship longitudinally, that is, whether wealthier adolescents are more likely than those with lower SES to engage in substance use in early adulthood.</p> <p>Methods</p> <p>The study analyzed data from the National Longitudinal Survey of Adolescent Health (AddHealth), a longitudinal, nationally-representative survey of secondary school students in the United States. Logistic regression models were analyzed examining the relationship between adolescent SES (measured by parental education and income) and substance use in adulthood, controlling for substance use in adolescence and other covariates.</p> <p>Results</p> <p>Higher parental education is associated with higher rates of binge drinking, marijuana and cocaine use in early adulthood. Higher parental income is associated with higher rates of binge drinking and marijuana use. No statistically significant results are found for crystal methamphetamine or other drug use. Results are not sensitive to the inclusion of college attendance by young adulthood as a sensitivity analysis. However, when stratifying by race, results are consistent for white non-Hispanics, but no statistically significant results are found for non-whites. This may be a reflection of the smaller sample size of non-whites, but may also reflect that these trends are driven primarily by white non-Hispanics.</p> <p>Conclusions</p> <p>Previous research shows numerous problems associated with substance use in young adults, including problems in school, decreased employment, increases in convictions of driving under the influence (DUI) and accidental deaths. Much of the previous literature is focused on lower SES populations. Therefore, it is possible that teachers, parents and school administrators in wealthier schools may not perceive as great to address substance abuse treatment in their schools. This study can inform teachers, parents, school administrators and program officials of the need for addressing drug abuse prevention activities to this population of students.</p

Search for short baseline nu(e) disappearance with the T2K near detector

8 pages, 6 figures, submitted to PRD rapid communication8 pages, 6 figures, submitted to PRD rapid communicationWe thank the J-PARC staff for superb accelerator performance and the CERN NA61 collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC and CFI, Canada; Commissariat `a l’Energie Atomique and Centre National de la Recherche Scientifique–Institut National de Physique Nucle´aire et de Physique des Particules, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; Russian Science Foundation, RFBR and Ministry of Education and Science, Russia; MINECO and European Regional Development Fund, Spain; Swiss National Science Foundation and State Secretariat for Education, Research and Innovation, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK. In addition participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; DOE Early Career program, USA

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011