Performance of a Large Area Avalanche Photodiode in a Liquid Xenon Ionization and Scintillation Chamber

Scintillation light produced in liquid xenon (LXe) by alpha particles, electrons and gamma-rays was detected with a large area avalanche photodiode (LAAPD) immersed in the liquid. The alpha scintillation yield was measured as a function of applied electric field. We estimate the quantum efficiency of the LAAPD to be 45%. The best energy resolution from the light measurement at zero electric field is 7.5%(sigma) for 976 keV internal conversion electrons from Bi-207 and 2.6%(sigma) for 5.5 MeV alpha particles from Am-241. The detector used for these measurements was also operated as a gridded ionization chamber to measure the charge yield. We confirm that using a LAAPD in LXe does not introduce impurities which inhibit the drifting of free electrons.Comment: 13 pages, 8 figure

Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database.

Utility of adjuvant chemotherapy for stage II cancer remains a matter of debate. Clinical guidelines suggest adjuvant chemotherapy for stage II tumors with high-risk features, in particular T4 tumors. However, limited consensus exists regarding the importance of other high-risk features (lymphovascular or perineural invasion, microsatellite instability). Our study aimed to investigate the impact of adjuvant chemotherapy for stage IIA (T3N0) colon cancer patients. Patients who underwent colectomy for stage IIA colon adenocarcinoma (2010-2015) were identified in the National Cancer Database (NCDB) and divided in two groups based on receipt of adjuvant chemotherapy vs observation. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed to compare overall survival between the two groups. Subgroup analysis of patients with specific high-risk features LVI, PNI and MSI was performed. Among 46 688 surgical patients with stage IIA colon adenocarcinoma 5937 (12.7%) received adjuvant chemotherapy, while 40 751 (87.3%) were observed. Five-year IPTW-adjusted survival was higher in the adjuvant chemotherapy group (79.7% [95% CI 79.1, 80.2]) compared to the observation group (70.3% [95% CI 69.7, 70.9]). Patients with high-risk pathological features showed an estimated 5-year survival benefit of 11.3% (78.2% [95% CI 77.4, 79.1] vs 66.9% [95% CI 65.9, 67.8]) when treated with adjuvant chemotherapy. This NCDB analysis revealed a survival benefit for patients with stage IIA colon adenocarcinoma and high-risk features that were treated with adjuvant chemotherapy

Developing the Active Communities Tool to Implement the Community Guide's Built Environment Recommendation for Increasing Physical Activity

Physical activity is higher in communities that include supportive features for walking and bicycling. In 2016, the Community Preventive Services Task Force released a systematic review of built environment approaches to increase physical activity. The results of the review recommended approaches that combine interventions to improve pedestrian and bicycle transportation systems with land use and environmental design strategies. Because the recommendation was multifaceted, the Centers for Disease Control and Prevention determined that communities could benefit from an assessment tool to address the breadth of the Task Force recommendations. The purpose of this article is to describe the systematic approach used to develop the Active Communities Tool. First, we created and refined a logic model and community theory of change for tool development. Second, we reviewed existing community-based tools and abstracted key elements (item domains, advantages, disadvantages, updates, costs, permissions to use, and psychometrics) from 42 tools. The review indicated that no tool encompassed the breadth of the Community Guide recommendations for communities. Third, we developed a new tool and pilot tested its use with 9 diverse teams with public health and planning expertise. Final revisions followed from pilot team and expert input. The Active Communities Tool comprises 6 modules addressing all 8 interventions recommended by the Task Force. The tool is designed to help cross-sector teams create an action plan for improving community built environments that promote physical activity and may help to monitor progress toward achieving community conditions known to promote physical activity

Evaluation of the Prescribing Skills Assessment implementation, performance and medical student experience in Australia and New Zealand

Aims: The UK Prescribing Safety Assessment was modified for use in Australia and New Zealand (ANZ) as the Prescribing Skills Assessment (PSA). We investigated the implementation, student performance and acceptability of the ANZ PSA for final-year medical students. Methods:This study used a mixed-method approach involving student data (n = 6440) for 2017–2019 (PSA overall score and 8 domain subscores). Data were also aggregated by medical school and included student evaluation survey results. Quantitative data were analysed using descriptive and multivariate analyses. The pass rate was established by a modified Angoff method. Thematic analyses of open-ended survey comments were conducted. Results:The average pass rate was slightly higher in 2017 (89%) which used a different examination to 2018 (85%) and 2019 (86%). Little difference was identified between schools for the PSA overall performance or domain subscores. There was low intercorrelation between subscores. Most students provided positive feedback about the PSA regarding the interface and clarity of questions, but an average of 35% reported insufficient time for completion. Further, 70% on average felt unprepared by their school curricula for the PSA, which is in part explained by the low prescribing experience; 69% reported completing ≤10 prescriptions during training. Conclusion:The ANZ PSA was associated with high pass rates and acceptability, although student preparedness was highlighted as a concern for further investigation. We demonstrate how a collaboration of medical schools can adapt a medical education assessment resource (UK PSA) as a means for fulfilling an unmet need.</p

Salt-induced expression of intracellular vesicle trafficking genes, CaRab-GTP, and their association with Na(+) accumulation in leaves of chickpea (Cicer arietinum L.)

Background: Chickpea is an important legume and is moderately tolerant to salinity stress during the growing season. However, the level and mechanisms for salinity tolerance can vary among accessions and cultivars. A large family of CaRab-GTP genes, previously identified in chickpea, is homologous to intracellular vesicle trafficking superfamily genes that play essential roles in response to salinity stress in plants. Results: To determine which of the gene family members are involved in the chickpea salt response, plants from six selected chickpea accessions (Genesis 836, Hattrick, ICC12726, Rupali, Slasher and Yubileiny) were exposed to salinity stress and expression profiles resolved for the major CaRab-GTP gene clades after 5, 9 and 15 days of salt exposure. Gene clade expression profiles (using degenerate primers targeting all members of each clade) were tested for their relationship to salinity tolerance measures, namely plant biomass and Na+ accumulation. Transcripts representing 11 out of the 13 CaRab clades could be detected by RT-PCR, but only six (CaRabA2, -B, -C, -D, -E and -H) could be quantified using qRT-PCR due to low expression levels or poor amplification efficiency of the degenerate primers for clades containing several gene members. Expression profiles of three gene clades, CaRabB, -D and -E, were very similar across all six chickpea accessions, showing a strongly coordinated network. Salt-induced enhancement of CaRabA2 expression at 15 days showed a very strong positive correlation (R2 = 0.905) with Na+ accumulation in leaves. However, salinity tolerance estimated as relative plant biomass production compared to controls, did not correlate with Na+ accumulation in leaves, nor with expression profiles of any of the investigated CaRab-GTP genes. Conclusion: A coordinated network of CaRab-GTP genes, which are likely involved in intracellular trafficking, are important for the salinity stress response of chickpea plants.Crystal Sweetman, Gulmira Khassanova, Troy K. Miller, Nicholas J. Booth, Akhylbek Kurishbayev, Satyvaldy Jatayev, Narendra K. Gupta, Peter Langridge, Colin L.D. Jenkins, Kathleen L. Soole, David A. Day and Yuri Shavruko

Measurement of the Nucleon Structure Function F2 in the Nuclear Medium and Evaluation of its Moments

We report on the measurement of inclusive electron scattering off a carbon target performed with CLAS at Jefferson Laboratory. A combination of three different beam energies 1.161, 2.261 and 4.461 GeV allowed us to reach an invariant mass of the final-state hadronic system W~2.4 GeV with four-momentum transfers Q2 ranging from 0.2 to 5 GeV2. These data, together with previous measurements of the inclusive electron scattering off proton and deuteron, which cover a similar continuous two-dimensional region of Q2 and Bjorken variable x, permit the study of nuclear modifications of the nucleon structure. By using these, as well as other world data, we evaluated the F2 structure function and its moments. Using an OPE-based twist expansion, we studied the Q2-evolution of the moments, obtaining a separation of the leading-twist and the total higher-twist terms. The carbon-to-deuteron ratio of the leading-twist contributions to the F2 moments exhibits the well known EMC effect, compatible with that discovered previously in x-space. The total higher-twist term in the carbon nucleus appears, although with large systematic uncertainites, to be smaller with respect to the deuteron case for n<7, suggesting partial parton deconfinement in nuclear matter. We speculate that the spatial extension of the nucleon is changed when it is immersed in the nuclear medium.Comment: 37 pages, 15 figure

Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10−8), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits

Quasielastic axial-vector mass from experiments on neutrino-nucleus scattering

We analyze available experimental data on the total and differential charged-current cross sections for quasielastic neutrino and antineutrino scattering off nucleons, measured with a variety of nuclear targets in the accelerator experiments at ANL, BNL, FNAL, CERN, and IHEP, dating from the end of sixties to the present day. The data are used to adjust the poorly known value of the axial-vector mass of the nucleon.Comment: 27 pages, 19 figures. Typos corrected; tables, figures and references added, discussion extended; matches published versio

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants