Planting the Seeds for Public Health: How the Farm Bill Can Help Farmers to Produce and Distribute Healthy Foods

Analyzes provisions in the 2008 Farm Bill that impede farmers' production and strategic marketing of fruits and vegetables. Recommends policy changes to remove such barriers, improve consumer access to healthy foods, and help prevent childhood obesity

Theoretical Evaluations of the Fission Cross Section of the 77 eV Isomer of 235-U

We have developed models of the fission barrier (barrier heights and transition state spectra) that reproduce reasonably well the measured fission cross section of $^{235}$U from neutron energy of 1 keV to 2 MeV. From these models we have calculated the fission cross section of the 77 eV isomer of $^{235}$U over the same energy range. We find that the ratio of the isomer cross section to that of the ground state lies between about 0.45 and 0.55 at low neutron energies. The cross sections become approximately equal above 1 MeV. The ratio of the neutron capture cross section to the fission cross section for the isomer is predicted to be about a factor of 3 larger for the isomer than for the ground state of $^{235}$U at keV neutron energies. We have also calculated the cross section for the population of the isomer by inelastic neutron scattering form the $^{235}$U ground state. We find that the isomer is strongly populated, and for $E_n = 1 MeV$ the $(n,n'\gamma)$ cross section leading to the population of the isomer is of the order of 0.5 barn. Thus, neutron reaction network calculations involving the uranium isotopes in a high neutron fluence are likely to be affected by the 77 eV isomer of $^{235}$U. With these same models the fission cross sections of $^{233}$U and $^{237}$U can be reproduced approximately using only minor adjustments to the barrier heights. With the significant lowering of the outer barrier that is expected for the outer barrier the general behavior of the fission cross section of $^{239}$Pu can also be reproduced.Comment: 17 pages including 8 figure

Whole Genome Amplification of DNA for Genotyping Pharmacogenetics Candidate Genes

Whole genome amplification (WGA) technologies can be used to amplify genomic DNA when only small amounts of DNA are available. The Multiple Displacement Amplification Phi polymerase based amplification has been shown to accurately amplify DNA for a variety of genotyping assays; however, it has not been tested for genotyping many of the clinically relevant genes important for pharmacogenetic studies, such as the cytochrome P450 genes, that are typically difficult to genotype due to multiple pseudogenes, copy number variations, and high similarity to other related genes. We evaluated whole genome amplified samples for Taqman™ genotyping of SNPs in a variety of pharmacogenetic genes. In 24 DNA samples from the Coriell human diversity panel, the call rates, and concordance between amplified (∼200-fold amplification) and unamplified samples was 100% for two SNPs in CYP2D6 and one in ESR1. In samples from a breast cancer clinical trial (Trial 1), we compared the genotyping results in samples before and after WGA for three SNPs in CYP2D6, one SNP in CYP2C19, one SNP in CYP19A1, two SNPs in ESR1, and two SNPs in ESR2. The concordance rates were all >97%. Finally, we compared the allele frequencies of 143 SNPs determined in Trial 1 (whole genome amplified DNA) to the allele frequencies determined in unamplified DNA samples from a separate trial (Trial 2) that enrolled a similar population. The call rates and allele frequencies between the two trials were 98 and 99.7%, respectively. We conclude that the whole genome amplified DNA is suitable for Taqman™ genotyping for a wide variety of pharmacogenetically relevant SNPs

Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors

PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured. RESULTS: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover. CONCLUSIONS: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI

Predicting phenotypes of beef eating quality traits

Introduction: Phenotype predictions of beef eating quality for individual animals could be used to allocate animals to longer and more expensive feeding regimes as they enter the feedlot if they are predicted to have higher eating quality, and to sort carcasses into consumer or market value categories. Phenotype predictions can include genetic effects (breed effects, heterosis and breeding value), predicted from genetic markers, as well as fixed effects such as days aged and carcass weight, hump height, ossification, and hormone growth promotant (HGP) status. Methods: Here we assessed accuracy of phenotype predictions for five eating quality traits (tenderness, juiciness, flavour, overall liking and MQ4) in striploins from 1701 animals from a wide variety of backgrounds, including Bos indicus and Bos taurus breeds, using genotypes and simple fixed effects including days aged and carcass weight. The genetic components were predicted based on 709k single nucleotide polymorphism (SNP) using BayesR model, which assumes some markers may have a moderate to large effect. Fixed effects in the prediction included principal components of the genomic relationship matrix, to account for breed effects, heterosis, days aged and carcass weight. Results and Discussion: A model which allowed breed effects to be captured in the SNP effects (e.g., not explicitly fitting these effects) tended to have slightly higher accuracies (0.43-0.50) compared to when these effects were explicitly fitted as fixed effects (0.42-0.49), perhaps because breed effects when explicitly fitted were estimated with more error than when incorporated into the (random) SNP effects. Adding estimates of effects of days aged and carcass weight did not increase the accuracy of phenotype predictions in this particular analysis. The accuracy of phenotype prediction for beef eating quality traits was sufficiently high that such predictions could be useful in predicting eating quality from DNA samples taken from an animal/carcass as it enters the processing plant, to enable optimal supply chain value extraction by sorting product into markets with different quality. The BayesR predictions identified several novel genes potentially associated with beef eating quality

Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer

PURPOSE: Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. METHODS: In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole (n = 241) or exemestane (n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. RESULTS: The ranges of baseline estrogen concentrations were <LLOQ-361 pg/mL for E2, <LLOQ-190 pg/mL for E1, and 8.3-4060 pg/mL for E1S. For E2, the frequency of suppression below the LLOQ was not statistically significantly different between AIs (exemestane: 89.0%, letrozole: 86.9%, p = 0.51). However, patients on letrozole were more likely to achieve suppression below the LLOQ of both E1 (exemestane: 80.1%, letrozole: 90.1%, p = 0.005) and E1S (exemestane: 17.4%, letrozole: 54.9%, p = 4.34e-15). After 3 months of AI therapy, the ranges of estrogen concentrations were <LLOQ-63.8 pg/mL, <LLOQ-36.7 pg/mL, and <LLOQ-1090 pg/mL for E2, E1, and E1S, respectively. During treatment, 16 patients had an increased concentration compared to the baseline concentration of at least one estrogen. CONCLUSIONS: Letrozole had greater suppression of plasma E1 and E1S than exemestane, though the response was highly variable among patients. Additional research is required to examine the clinical relevance of differential estrogen suppression

Genetic variation in EPHA contributes to sensitivity to paclitaxel‐induced peripheral neuropathy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154957/1/bcp14192.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154957/2/bcp14192_am.pd

IL-12p70–producing patient DC vaccine elicits Tc1-polarized immunity

Background. Systemic administration of IL-12p70 has demonstrated clinical activity in cancer patients, but dose-limiting toxicities have hindered its incorporation in vaccine formulations. Here, we report on the immunological and clinical outcomes upon vaccination with CD40L/IFN-γ–matured, IL-12p70–producing DCs. Methods. 7 HLA-A*0201(+) newly diagnosed stage IV melanoma patients were immunized against the gp100 melanoma antigen using autologous peptide-pulsed, CD40L/IFN-γ–matured DCs. PBMCs were taken weekly for immune monitoring by tetramer analysis and functional assays. CT imaging was performed at baseline, week 9, and week 18 for clinical assessment using RECIST. Results. 6 of 7 treated patients developed sustained T cell immunity to all 3 melanoma gp100 antigen–derived peptides. 3 of the 6 immunological responders developed confirmed clinical responses (1 complete remission >4 years, 2 partial response). Importantly, DC vaccine–derived IL-12p70 levels positively correlated with time to progression (P = 0.019, log-rank), as did T-cytotoxic 1 (Tc1) immunity, as assessed by IFN-γ/IL-13 and IFN-γ/IL-5 ratios (P = 0.035 and P = 0.030, respectively, log-rank). In contrast, a pathway-specific defect in IL-12p35 transcription was identified upon CD40L/IFN-γ activation in clinical nonresponder patient DCs, and gp100-specific T cells from these patients displayed a Tc2 phenotype. Incorporation of TLR3 and TLR8 agonists into the CD40L/IFN-γ activation protocol corrected the IL-12p70 production defect in DCs derived from clinical nonresponder patients. Conclusion. These findings underscore the essential role of IL-12p70 in the development of therapeutic type 1 antigen–specific CD8(+) T cell immunity in humans with cancer. Trial registration. Clinicaltrials.gov NCT00683670. Funding. Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Washington University/JNJ Translational Medicine Award, and NCI (P30 CA91842)

From Quantum Systems to L-Functions: Pair Correlation Statistics and Beyond

The discovery of connections between the distribution of energy levels of heavy nuclei and spacings between prime numbers has been one of the most surprising and fruitful observations in the twentieth century. The connection between the two areas was first observed through Montgomery's work on the pair correlation of zeros of the Riemann zeta function. As its generalizations and consequences have motivated much of the following work, and to this day remains one of the most important outstanding conjectures in the field, it occupies a central role in our discussion below. We describe some of the many techniques and results from the past sixty years, especially the important roles played by numerical and experimental investigations, that led to the discovery of the connections and progress towards understanding the behaviors. In our survey of these two areas, we describe the common mathematics that explains the remarkable universality. We conclude with some thoughts on what might lie ahead in the pair correlation of zeros of the zeta function, and other similar quantities.Comment: Version 1.1, 50 pages, 6 figures. To appear in "Open Problems in Mathematics", Editors John Nash and Michael Th. Rassias. arXiv admin note: text overlap with arXiv:0909.491

Can the internet reduce the loneliness of 50+ living alone?

Published online: 12 May 2020Living alone has been indicated as a key variable to explain loneliness in older adults. In contemporary society, where technology has become one of the main means of communication and personal interaction, has the internet influenced the relationship between living alone and loneliness? This paper aims to answer this research question by using a sample of 64,297 individuals who were surveyed in SHARE project wave 6 – in European countries with different welfare regimes (Portugal, Greece, Italy and Spain, Denmark, Sweden, Austria, Belgium, France, Germany, Switzerland, Luxemburg, Poland, Czech Republic; Slovenia, Estonia, and Croatia). The results of the regression analysis evidence the moderating role of the internet on the relationship between living alone and feelings of loneliness in individuals aged 50 and over, so that the impact of living alone on loneliness is diminished for internet users as compared to their peers who do not use the internet. The results therefore reinforce the importance of policies aimed at fostering e-inclusion as a way of reducing the loneliness of older adultsThis work was supported by European Commission; Fundação para a Ciência e a Tecnologia; U.S National Institute on Aging; Fundação Calouste Gulbenkian; German Ministry of Education and Researc