2,771 research outputs found
Transverse Spin Structure of the Nucleon through Target Single Spin Asymmetry in Semi-Inclusive Deep-Inelastic Reaction at Jefferson Lab
Jefferson Lab (JLab) 12 GeV energy upgrade provides a golden opportunity to
perform precision studies of the transverse spin and
transverse-momentum-dependent structure in the valence quark region for both
the proton and the neutron. In this paper, we focus our discussion on a
recently approved experiment on the neutron as an example of the precision
studies planned at JLab. The new experiment will perform precision measurements
of target Single Spin Asymmetries (SSA) from semi-inclusive electro-production
of charged pions from a 40-cm long transversely polarized He target in
Deep-Inelastic-Scattering kinematics using 11 and 8.8 GeV electron beams. This
new coincidence experiment in Hall A will employ a newly proposed solenoid
spectrometer (SoLID). The large acceptance spectrometer and the high polarized
luminosity will provide precise 4-D (, , and ) data on the
Collins, Sivers, and pretzelocity asymmetries for the neutron through the
azimuthal angular dependence. The full 2 azimuthal angular coverage in the
lab is essential in controlling the systematic uncertainties. The results from
this experiment, when combined with the proton Collins asymmetry measurement
and the Collins fragmentation function determined from the ee collision
data, will allow for a quark flavor separation in order to achieve a
determination of the tensor charge of the d quark to a 10% accuracy. The
extracted Sivers and pretzelocity asymmetries will provide important
information to understand the correlations between the quark orbital angular
momentum and the nucleon spin and between the quark spin and nucleon spin.Comment: 23 pages, 13 figures, minor corrections, matches published versio
Heart failure and patient-reported outcomes in adults with congenital heart disease from 15 countries
Background Heart failure (HF) is the leading cause of mortality and associated with significant morbidity in adults with congenital heart disease. We sought to assess the association between HF and patient-report outcomes in adults with congenital heart disease. Methods and Results As part of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study), we collected data on HF status and patient-reported outcomes in 3959 patients from 15 countries across 5 continents. Patient-report outcomes were: perceived health status (12-item Short Form Health Survey), quality of life (Linear Analogue Scale and Satisfaction with Life Scale), sense of coherence-13, psychological distress (Hospital Anxiety and Depression Scale), and illness perception (Brief Illness Perception Questionnaire). In this sample, 137 (3.5%) had HF at the time of investigation, 298 (7.5%) had a history of HF, and 3524 (89.0%) had no current or past episode of HF. Patients with current or past HF were older and had a higher prevalence of complex congenital heart disease, arrhythmias, implantable cardioverter-defibrillators, other clinical comorbidities, and mood disorders than those who never had HF. Patients with HF had worse physical functioning, mental functioning, quality of life, satisfaction with life, sense of coherence, depressive symptoms, and illness perception scores. Magnitudes of differences were large for physical functioning and illness perception and moderate for mental functioning, quality of life, and depressive symptoms. Conclusions HF in adults with congenital heart disease is associated with poorer patient-reported outcomes, with large effect sizes for physical functioning and illness perception. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02150603
Membrane inlet mass spectrometry method (REOX/MIMS) to measure 15N-nitrate in isotope-enrichment experiments
Using 15N stable isotope as a tracer to quantify N transformation rates in isotope-enrichment experiments improves understanding of the N cycle in various ecosystems. However, measuring 15N-nitrate (15NO3−) in small volumes of water for these experiments is a major challenge due to the inconvenience of preparing samples by traditional techniques. We developed a “REOX/MIMS” method by applying membrane inlet mass spectrometry (MIMS) to determining 15NO3− concentrations in a small volumes of water from isotope-enrichment experiments after converting the dissolved inorganic N to N2. The nitrates (NO3− + NO2−) were reduced to NH4+ with zinc powder, and the ammonium (NH4+) was then oxidized to N2 by hypobromite iodine solution. The resulting 29N2 and 30N2 were measured via MIMS. This optimized protocol provides a sensitive (~0.1 μM) and precise (relative standard deviation = 0.1–4.37%) approach to quantify 15NO3− concentrations (0.1–500 µM) in water samples over a wide range of salinities (0–35‰) and in 2 M KCl solution with excellent calibration curves (R2 ≥ 0.9996, p \u3c 0.0001). The method was combined with 15NO3− isotope-enrichment incubation experiments to measure gross nitrification and gross NO3− immobilization rates in various ecosystems. It was rapid, accurate, and cost-effective. Future applications of this efficient approach will inform scientists, modelers and decision makers about mechanisms, sources, fates, and effects of NO3− delivered to or produced in numerous aquatic and terrestrial ecosystems
Insurance Coverage Policies for Pharmacogenomic and Multi-Gene Testing for Cancer
Abstract: Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests. Coverage for KRAS, EGFR, and BRAF tests were common across Medicare contractors and private payers, but few policies covered PML/RARA, CD25, or G6PD. Twelve payers cover at least one multi-gene test for nonsmall cell lung cancer, citing emerging clinical recommendations. Coverage policies for single and multi-gene tests for cancer treatments are relatively consistent among Medicare contractors despite the lack of national coverage determinations. In contrast, coverage for these tests varied across private payers. Patient access to tests is governed by prior authorization among eight private payers. Substantial variations in how payers address guideline-recommended pharmacogenomic tests and the common use of prior authorization underscore the need for additional studies of the effects of coverage variation on cancer care and patient outcomes
Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma
Comparative LD mapping using single SNPs and haplotypes identifies QTL for plant height and biomass as secondary traits of drought tolerance in maize
Drought often delays developmental
events so that plant height and above-ground biomass
are reduced, resulting in yield loss due to inadequate
photosynthate. In this study, plant height and biomass
measured by the Normalized Difference Vegetation
Index (NDVI) were used as criteria for drought
tolerance. A total of 305 lines representing temperate,
tropical and subtropical maize germplasm were genotyped
using two single nucleotide polymorphism
(SNP) chips each containing 1536 markers, from
which 2052 informative SNPs and 386 haplotypes
each constructed with two or more SNPs were used for
linkage disequilibrium (LD) or association mapping.
Single SNP- and haplotype-based LD mapping identified
two significant SNPs and three haplotype loci [a
total of four quantitative trait loci (QTL)] for plantheight under well-watered and water-stressed conditions.
For biomass, 32 SNPs and 12 haplotype loci (30
QTL) were identified using NDVIs measured at seven
stages under the two water regimes. Some significant
SNP and haplotype loci for NDVI were shared by
different stages. Comparing significant loci identified
by single SNP- and haplotype-based LD mapping, we
found that six out of the 14 chromosomal regions
defined by haplotype loci each included at least one
significant SNP for the same trait. Significant SNP
haplotype loci explained much higher phenotypic
variation than individual SNPs. Moreover, we found
that two significant SNPs (two QTL) and one haplotype
locus were shared by plant height and NDVI. The
results indicate the power of comparative LD mapping
using single SNPs and SNP haplotypes with QTL
shared by plant height and biomass as secondary traits for drought tolerance in maize
Combining Multiple Serum Biomarkers in Tumor Diagnosis: A Clinical Assessment
The present study aimed to assess the diagnostic/ prognostic value of various clinical tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA21-1), α-fetoprotein (AFP), carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9) and ferritin, individually or in combination. The electro-chemiluminescence immunization method was performed to detect the levels of seven tumor markers in 560 cancer patients and 103 healthy subjects for comparison. The serum levels of the seven markers measured in cancer patients were higher compared to healthy subjects (P<0.05 for AFP and P<0.001 for the remaining six markers). Different markers had different sensitivity towards different types of tumors. Combining more markers significantly increased the ratios of positive diagnosis in the tumors. The diagnostic sensitivities of combining seven markers were particularly high in digestive, urinary and skeletal tumors (82, 92 and 83%, respectively). Gynecological tumors have exhibited a constant yet relatively low positive diagnosis irrespective of the use of a single marker or combined markers. However, the increase in sensitivity when combining markers was accompanied by a decrease in specificity. Generally, combining more markers increased the tumor detection rates, while a combination of the seven markers provided the highest detection rate. Combined detection showed a particularly high sensitivity in detecting respiratory, digestive and urinary system tumors, with the lowest sensitivity observed in gynecological tumors. As a result, combining tumor markers may play an important role in early tumor detection/diagnosis while the loss of specificity can be tolerated
Neoplastic cell enrichment of tumor tissues using coring and laser microdissection for proteomic and genomic analyses of pancreatic ductal adenocarcinoma
BACKGROUND: The identification of differentially expressed tumor-associated proteins and genomic alterations driving neoplasia is critical in the development of clinical assays to detect cancers and forms the foundation for understanding cancer biology. One of the challenges in the analysis of pancreatic ductal adenocarcinoma (PDAC) is the low neoplastic cellularity and heterogeneous composition of bulk tumors. To enrich neoplastic cells from bulk tumor tissue, coring, and laser microdissection (LMD) sampling techniques have been employed. In this study, we assessed the protein and KRAS mutation changes associated with samples obtained by these enrichment techniques and evaluated the fraction of neoplastic cells in PDAC for proteomic and genomic analyses.
METHODS: Three fresh frozen PDAC tumors and their tumor-matched normal adjacent tissues (NATs) were obtained from three sampling techniques using bulk, coring, and LMD; and analyzed by TMT-based quantitative proteomics. The protein profiles and characterizations of differentially expressed proteins in three sampling groups were determined. These three PDACs and samples of five additional PDACs obtained by the same three sampling techniques were also subjected to genomic analysis to characterize KRAS mutations.
RESULTS: The neoplastic cellularity of eight PDACs ranged from less than 10% to over 80% based on morphological review. Distinctive proteomic patterns and abundances of certain tumor-associated proteins were revealed when comparing the tumors and NATs by different sampling techniques. Coring and bulk tissues had comparable proteome profiles, while LMD samples had the most distinct proteome composition compared to bulk tissues. Further genomic analysis of bulk, cored, or LMD samples demonstrated that KRAS mutations were significantly enriched in LMD samples while coring was less effective in enriching for KRAS mutations when bulk tissues contained a relatively low neoplastic cellularity.
CONCLUSIONS: In addition to bulk tissues, samples from LMD and coring techniques can be used for proteogenomic studies. The greatest enrichment of neoplastic cellularity is obtained with the LMD technique
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