Multivariate genomic analysis and optimal contributions selection predicts high genetic gains in cooking time, iron, zinc, and grain yield in common beans in East Africa.

Common bean (Phaseolus vulgaris L.) is important in African diets for protein, iron (Fe), and zinc (Zn), but traditional cultivars have long cooking time (CKT), which increases the time, energy, and health costs of cooking. Genomic selection was used to predict genomic estimated breeding values (GEBV) for grain yield (GY), CKT, Fe, and Zn in an African bean panel of 358 genotypes in a two-stage analysis. In Stage 1, best linear unbiased estimates (BLUE) for each trait were obtained from 898 genotypes across 33 field trials in East Africa. In Stage 2, BLUE in a training population of 141 genotypes were used in a multivariate genomic analysis with genome-wide single nucleotide polymorphism data from the African bean panel. Moderate to high genomic heritability was found for GY (0.45 ± 0.10), CKT (0.50 ± 0.15), Fe (0.57 ± 0.12), and Zn (0.61 ± 0.13). There were significant favorable genetic correlations between Fe and Zn (0.91 ± 0.06), GY and Fe (0.66 ± 0.17), GY and Zn (0.44 ± 0.19), CKT and Fe (-0.57 ± 0.21), and CKT and Zn (-0.67 ± 0.20). Optimal contributions selection (OCS), based on economic index of weighted GEBV for each trait, was used to design crossing within four market groups relevant to East Africa. Progeny were predicted by OCS to increase in mean GY by 12.4%, decrease in mean CKT by 9.3%, and increase in mean Fe and Zn content by 6.9 and 4.6%, respectively, with low achieved coancestry of 0.032. Genomic selection with OCS will accelerate breeding of high-yielding, biofortified, and rapid cooking African common bean cultivars.

Comparison of Physician Data in Two Data Files Available for Cancer Health Services Research.

INTRODUCTION: Physicians are vital to health-care delivery, but assessing their impact on care can be challenging given limited data. Historically, health services researchers have obtained physician characteristics data from the American Medical Association (AMA) Physician Masterfile. The Center for Medicare and Medicaid Services' Medicare Data on Provider Practice and Specialty (MD-PPAS) file was assessed, as an alternative source of physician data, particularly in the context of cancer health services research. METHODS: We used physician National Provider Identifiers in the MD-PPAS data (2008-2014) to identify physicians in the AMA data current as of July 18, 2016. Within each source, we grouped physicians into six broad specialty groups. Percent agreement and Cohen's kappa coefficient (k) were calculated for age, sex, specialty, and practice state. RESULTS: Among the 698 202 included physicians, there was excellent agreement for age (percent agreement = 97.7%, k = 0.97) and sex (99.4%, k = 0.99) and good agreement for specialty (86.1%, k = 0.80). Within specialty, using AMA as the reference, agreement was lowest for oncologists (77%). Approximately 85.9% of physicians reported the same practice state in both data sets. CONCLUSION: Although AMA data have been commonly used to account for physician-level factors in health services research, MD-PPAS data provide researchers with an alternative option depending on study needs. MD-PPAS data may be optimal if nonphysicians, provider utilization, practice characteristics, and/or temporal changes are of interest. In contrast, the AMA data may be optimal if more granular specialty, physician training, and/or a broader inclusion of physicians is of interest.

Sensitivity of Medicare Data to Identify Oncologists.

BACKGROUND: Health services researchers have studied how care from oncologists impacts treatment and outcomes for cancer patients. These studies frequently identify physician specialty using files from the Center for Medicare and Medicaid Services (CMS) or the American Medical Association (AMA). The completeness of the CMS data resources, individually or combined, to identify oncologists is unknown. This study assessed the sensitivity of CMS data to capture oncologists included in the AMA Physician Masterfile. METHODS: Oncologists were identified from three CMS data resources: physician claims, the National Plan and Provider Enumeration System Registry, and the Medicare Data on Provider Practice and Specialty file. CMS files and AMA data were linked using a unique physician identifier. Sensitivity to identify any oncologists, radiation oncologists (ROs), surgical oncologists (SOs), and medical oncologists (MOs) was calculated for individual and combined CMS files. For oncologists in the AMA data not identified as oncologists in the CMS data, their CMS specialty was assessed. RESULTS: Individual CMS files each captured approximately 83% of the 17 934 oncologists in the AMA Masterfile; combined CMS files captured 90.4%. By specialty, combined CMS data captured 98.2% of ROs, 89.3% of MOs, and 70.1% of SOs. For ROs and SOs in the AMA data not identified as oncologists in the CMS data, their CMS specialty was usually similar to the AMA subspecialty; ROs were radiologists and SOs were surgeons. CONCLUSION: Using combined files from CMS identified most ROs and MOs found in the AMA, but not most SOs. Determining whether to use the AMA data or CMS files for a particular research project will depend on the specific research question and the type of oncologist included in the study.

Creating a National Provider Identifier (NPI) to Unique Physician Identification Number (UPIN) Crosswalk for Medicare Data.

INTRODUCTION: Many health services researchers are interested in assessing long term, individual physician treatment patterns, particularly for cancer care. In 2007, Medicare changed the physician identifier used on billed services from the Unique Physician Identification Number (UPIN) to the National Provider Identifier (NPI), precluding the ability to use Medicare claims data to evaluate individual physician treatment patterns across this transition period. METHODS: Using the 2007-2008 carrier (physician) claims from the linked Surveillance, Epidemiology and End Results (SEER) cancer registry-Medicare data and Medicare's NPI and UPIN Directories, we created a crosswalk that paired physician NPIs included in SEER-Medicare data with UPINs. We evaluated the ability to identify an NPI-UPIN match by physician sex and specialty. RESULTS: We identified 470,313 unique NPIs in the 2007-2008 SEER-Medicare carrier claims and found a UPIN match for 90.1% of these NPIs (n=423,842) based on 3 approaches: (1) NPI and UPIN coreported on the SEER-Medicare claims; (2) UPINs reported on the NPI Directory; or (3) a name match between the NPI and UPIN Directories. A total of 46.6% (n=219,315) of NPIs matched to the same UPIN across all 3 approaches, 34.1% (n=160,277) agreed across 2 approaches, and 9.4% (n=44,250) had a match identified by 1 approach only. NPIs were paired to UPINs less frequently for women and primary care physicians compared with other specialists. DISCUSSION: National Cancer Institute has created a crosswalk resource available to researchers that links NPIs and UPINs based on the SEER-Medicare data. In addition, the documented process could be used to create other NPI-UPIN crosswalks using data beyond SEER-Medicare.

Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer.

Studies have shown enhanced survival of ovarian cancer patients in which the tumors are infiltrated with tumor infiltrating lymphocytes and natural killer cells showing the importance of immune surveillance and recognition in ovarian cancer. Therefore, in this study, we tested cellular immunotherapy and varying combinations of cytokines (IL-2 and/or pegylated-IFNα-2b) in a xenograft mouse model of ovarian cancer. SKOV3-AF2 ovarian cancer cells were injected intra-peritoneally (IP) into athymic nude mice. On day 7 post-tumor cell injection, mice were injected IP with peripheral blood mononuclear cells (PBMC; 5 × 10(6) PBMC) and cytokine combinations [IL-2 ± pegylated-IFNα-2b (IFN)]. Cytokine injections were continued weekly for IFN (12,000 U/injection) and thrice weekly for IL-2 (4000 U/injection). Mice were euthanized when they became moribund due to tumor burden at which time tumor and ascitic fluid were measured and collected. Treatment efficacy was measured by improved survival at 8 weeks and overall survival by Kaplan-Meier analysis. We observed that the mice tolerated all treatment combinations without significant weight loss or other apparent illness. Mice receiving PBMC plus IL-2 showed improved median survival (7.3 weeks) compared to mice with no treatment (4.2 weeks), IL-2 (3.5 weeks), PBMC (4.0 weeks), or PBMC plus IL-2 and IFN (4.3 weeks), although PBMC plus IL-2 was not statistically different than PBMC plus IFN (5.5 weeks, p > 0.05). We demonstrate that cytokine-stimulated cellular immune therapy with PBMC and IL-2 was well tolerated and resulted in survival advantage compared to untreated controls and other cytokine combinations in the nude-mouse model.

Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery.

Cholera and malaria are major diseases causing high mortality. The only licensed cholera vaccine is expensive; immunity is lost in children within 3 years and adults are not fully protected. No vaccine is yet available for malaria. Therefore, in this study, the cholera toxin-B subunit (CTB) of Vibrio cholerae fused to malarial vaccine antigens apical membrane antigen-1 (AMA1) and merozoite surface protein-1 (MSP1) was expressed in lettuce and tobacco chloroplasts. Southern blot analysis confirmed homoplasmy and stable integration of transgenes. CTB-AMA1 and CTB-MSP1 fusion proteins accumulated up to 13.17% and 10.11% (total soluble protein, TSP) in tobacco and up to 7.3% and 6.1% (TSP) in lettuce, respectively. Nine groups of mice (n = 10/group) were immunized subcutaneously (SQV) or orally (ORV) with purified antigens or transplastomic tobacco leaves. Significant levels of antigen-specific antibody titres of immunized mice completely inhibited proliferation of the malarial parasite and cross-reacted with the native parasite proteins in immunoblots and immunofluorescence studies. Protection against cholera toxin challenge in both ORV (100%) and SQV (89%) mice correlated with CTB-specific titres of intestinal, serum IgA and IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. Increasing numbers of interleukin-10(+) T cell but not Foxp3(+) regulatory T cells, suppression of interferon-gamma and absence of interleukin-17 were observed in protected mice, suggesting that immunity is conferred via the Tr1/Th2 immune response. Dual immunity against two major infectious diseases provided by chloroplast-derived vaccine antigens for long-term (>300 days, 50% of mouse life span) offers a realistic platform for low cost vaccines and insight into mucosal and systemic immunity.

Cancer mortality among butchers: a 24-state death certificate study.

OBJECTIVE: The objective of this study was to document cancer mortality among American butchers. METHODS: Death certificates collected in 24 American states were used to calculate mortality odds ratios (ORs) and their confidence intervals (CIs) for 18,639 butchers. RESULTS: Butchers experienced an increased mortality of cancer of the oral cavity (OR, 1.40; 95% CI = 1.09-1.81), esophagus (OR, 1.19; 95% CI = 1.01-1.40), pharynx (OR, 1.22; 95% CI = 0.91-1.64), and larynx (OR, 1.19; 95% CI = 0.92-1.54), as well as a reduced mortality from melanoma (OR, 0.70; 95% CI = 0.52-0.94), non-Hodgkin lymphoma (OR, 0.82; 95% CI = 0.69-0.97), and breast cancer (OR, 0.76; 95% CI = 0.58-0.99). CONCLUSIONS: It is likely that occupational exposures experienced by butchers have contributed to the increased risk of cancers of the oral cavity and esophagus.

Temporal trends and misclassification in residential 60 Hz magnetic field measurements.

This research addressed the question of how well measurement data collected during a single visit, made at an arbitrary hour of day, day of week, and season, estimate longer term residential 60 Hz magnetic field levels. We made repeat spot and 24 h measurements in 51 children's home, located in the Detroit, MI, and the Minneapolis-St. Paul, MN metropolitan areas, on a regular bimonthly schedule over a 1 year period, as well as a single 2 week measurement, for total of eight visits, producing 21 days of data for each residence. We defined the long term estimate (LTE) as the geometric mean of all available 24 h geometric means from the first six bimonthly visits. The LTE served as the reference level for assessing seasonal, day of week, and diurnal effects, as well as the potential for misclassification. We found a small, but statistically significant (P<.05), seasonal effect, with levels approximately 3% lower than the LTE in the spring and about 4% greater during the summer. No effect was found for day of week. However, we did find a systematic and appreciable diurnal effect, suggesting that, for example, an evening spot measurement may overestimate the LTE by 20% or more. We also assessed how well the 24 h measurement from the last visit, which was not used in calculation of the LTE, estimated the LTE. We found a high degree of correlation (r=.92) and fair to good agreement using four exposure categories (kappa=.53). Thus, the 24 h measurement appears to be a satisfactory LTE estimator. However, this finding must be interpreted with caution since considerable unexplained variability was present among the repeat 24 h measurements in about one-third of the homes. While the 2 week measurement does somewhat decrease exposure misclassification, its added intrusiveness and cost are likely to outweigh the improved precision.