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Reproductive information since 1995 from the USDA national dairy database was used to calculate yearly Holstein and Jersey means for days to first breeding after calving (DFB), 70-d nonreturn rate, conception rate (CR), number of breedings per lactation (NB), interval between first and last breedings during the lactation, days to last breeding after calving (DLB), pregnancy rate (PR), calving interval (CI), and interval between consecutive breedings. Data were from nearly 20million breedings during >8million lactations of >5million cows in >23,000 herds. Means were also calculated for some traits by parity and breeding number for both breeds and by geographical region and synchronization status for Holsteins. The DFB declined for Holsteins from 92 d in 1996 to 85 d in 2007; the trend in yearly differences was not as consistent for Jerseys. First- and all-breeding 70-d nonreturn rate declined 5 to 9 percentage units over time. First- and all-breeding CR declined 2 to 4 percentage units. The DFB were longer for later parities of Holsteins than for early parities. Second- and third-breeding CR were sometimes 1 to 2 percentage units above first-breeding CR for Holsteins but lower (1 to 7 percentage units) for Jerseys. The CR within breeding number declined across parities for both breeds. The NB increased by 0.3 to 0.4 breedings over time but remained constant (2.5 or 2.6 breedings) across parities for Holsteins and increased (from 2.2 to 2.4 breedings) for Jerseys. Holstein DFB were fewest in the Northwest (78 d) and greatest in the Mountain region (92 d). Regional CR was highest for the Northeast and Southwest (33%) and lowest for the Southeast (26%); NB was fewest for the Northeast (2.3) and greatest for the Southeast (2.7). Mean DLB was fewest for the Southwest (127 d) and greatest for the Mountain region (157 d); CI was shortest for the Southwest (406 d) and longest for the Mideast (434 d). Mean PR was highest for the Southwest (28.3%) and lowest for the Mideast and Southeast (22.2%). Use of timed artificial insemination following synchronized estrus appears to have reduced DFB, lowered CR, and increased NB while reducing DLB and CI. However, synchronized breeding was not a primary cause of Holstein regional differences for reproductive traits. Since 2002, phenotypic performance for CR, DLB, and CI as well as genetic merit for daughter PR have stopped their historical declines and started to improve.

Genetic and environmental factors that might affect gestation length (GL) were investigated. Data included information from >11million parturitions from 1999 through 2006 for 7 US dairy breeds. Effects examined were year, herd-year, month, and age within parity of conception; parturition code (sex and multiple-birth status); lactation length and standardized milk yield of cow; service sire; cow sire; and cow. All effects were fixed except for service sire, cow sire, and cow. Mean GL for heifers and cows, respectively, were 277.8 and 279.4 d for Holsteins, 278.4 and 280.0 d for Jerseys, 279.3 and 281.1 d for Milking Shorthorns, 281.6 and 281.7 d for Ayrshires, 284.8 and 285.7 d for Guernseys, and 287.2 and 287.5 d for Brown Swiss. Estimated standard deviations of GL were greatly affected by data restrictions but generally were approximately 5 to 6 d. Year effects on GL were extremely small, but month effects were moderate. For Holstein cows, GL was 2.0 d shorter for October conceptions than for January and February conceptions; 4.7 and 5.6 d shorter for multiple births of the same sex than for single-birth females and males, respectively; 0.8 d longer for lactations of ≤250 d than for lactations of ≥501 d; and 0.6 d shorter for standardized yield of ≤8,000kg than for yield of ≥14,001kg. Estimates for GL heritability from parities 2 to 5 were 33 to 36% for service sire and 7 to 12% for cow sire; corresponding estimates from parity 1 were 46 to 47% and 10 to 12%. Estimates of genetic correlations between effects of service sire and cow sire on GL were 0.70 to 0.85 for Brown Swiss, Holsteins, and Jerseys, which indicates that those traits likely are controlled by many of the same genes and can be used to evaluate each other. More accurate prediction of calving dates can help dairy producers to meet management requirements of pregnant animals and to administer better health care during high-risk phases of animals’ lives. However, intentional selection for either shorter or longer GL is not recommended without consideration of its possible effect on other dependent traits (e.g., calving ease and stillbirth).

Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit–granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed ( n =28) and unexposed ( n =14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared with levels in the control subjects ( P =0.0055 and P =0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 p.p.m. (20%, P =0.0419 and 28%, P =0.0056, respectively) and ⩾10 p.p.m. (48%, P =0.0045 and 32%, 0.0354) benzene, compared with controls, and significant exposure–response trends were detected ( P trend =0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood progenitor cells of workers exposed to benzene, and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens.

OBJECTIVES:Studies of cancer recurrences and second primary tumors require information on outcome dates. Little is known about how well electronic health record–based algorithms can identify dates or how errors in dates can bias analyses. RESEARCH DESIGN:We assessed rule-based and model-fitting approaches to assign event dates using a previously published electronic health record-based algorithm for second breast cancer events (SBCE). We conducted a simulation study to assess bias due to date assignment errors in time-to-event analyses. SUBJECTS:From a cohort of 3152 early-stage breast cancer patients, 358 women accurately identified as having had an SBCE served as the basis for this analysis. MEASURES:Percent of predicted SBCE dates identified within ±60 days of the true date was the primary measure of accuracy. In the simulation study, bias in hazard ratios (HRs) was estimated by averaging the difference between HRs based on algorithm-assigned dates and the true HR across 1000 simulations each with simulated N=4000. RESULTS:The most accurate date algorithm had a median difference between the true and predicted dates of 0 days with 82% of predicted dates falling within 60 days of the true date. Bias resulted when algorithm sensitivity and specificity varied by exposure status, but was minimal when date assignment errors were of the magnitude observed for our date assignment method. CONCLUSIONS:SBCE date can be relatively accurately assigned based on a previous algorithm. While acceptable in many scenarios, algorithm-assigned dates are not appropriate to use when operating characteristics are likely to vary by the study exposure.

PurposeThe survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial.MethodsWe followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I–III) from 2/2005–6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model.Results917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72–1.12) compared to those without MRI.ConclusionOur findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women’s decision quality and confidence levels with decisions involving treatment choices.

Preoperative magnetic resonance imaging (MRI) use has increased among older women diagnosed with breast cancer. MRI detects additional malignancy, but its impact on locoregional surgery and radiation treatment remains unclear. We examined the associations of preoperative MRI with initial locoregional treatment type (mastectomy, breast conserving surgery [BCS] with radiation therapy [RT], and BCS without RT) and BCS reoperation rates for Surveillance, Epidemiology, and End Results Medicare women diagnosed with stages 0 to III breast cancer from 2005 to 2009 (n = 55,997). We found no association of initial locoregional treatment of mastectomy (odds ratios [OR], 1.04; 95% confidence intervals, .98 to 1.11) or reoperation after initial BCS (OR, .96; 95% confidence intervals, .89 to 1.03) between women with preoperative MRI (16.2%) compared to women without MRI. However, women with MRI who had initial BCS were more likely to undergo RT (OR, 1.09 [1.02 to 1.16]). Preoperative breast MRI in Medicare-enrolled women with stages 0 to III breast cancer was not associated with increased mastectomy. However, in older women with MRI undergoing BCS, there was a greater use of RT. •Preoperative MRI in women stage 0-III breast cancer does not increase mastectomy.•There was a greater use of radiation therapy in older women with MRI undergoing BCS.•Results mitigate concerns about unnecessary MRI-associated mastectomies.

•Cumulative false-positive risks are >3 times higher in US compared to Denmark.•Model-based cumulative estimates are fairly similar to empirical estimates.•Screening intervals and mammogram type does not explain the differences.•Cumulative false-positive risks are fairly similar regardless of statistical method.•Independence between screens might be an acceptable assumption in US and Denmark. In the United States (US), about one-half of women screened with annual mammography have at least one false-positive test after ten screens. The estimate for European women screened ten times biennially is much lower. We evaluate to what extent screening interval, mammogram type, and statistical methods, can explain the reported differences. We included all screens from women first screened at age 50–69 years in the US Breast Cancer Surveillance Consortium (BCSC) (n=99,455) between 1996–2010, and from two population-based mammography screening programs in Denmark (n=230,452 and n=400,204), between 1991–2012 and 1993–2013, respectively. Model-based cumulative false-positive risks were computed for the entire sample, using two statistical methods (Hubbard Njor) previously used to estimate false-positive risks in the US and Europe. Empirical cumulative risk of at least one false-positive test after eight (annual or biennial) screens was 41.9% in BCSC, 16.1% in Copenhagen, and 7.4% in Funen. Variation in screening interval and mammogram type did not explain the differences by country. Using the Hubbard method, the model-based cumulative risks after eight screens was 45.1% in BCSC, 9.6% in Copenhagen, and 8.8% in Funen. Using the Njor method, these risks were estimated to be 43.6, 10.9 and 8.0%. Choice of statistical method, screening interval and mammogram type does not explain the substantial differences in cumulative false-positive risk between the US and Europe.

Background/aims: To assess the variability in retinal vessel measurements at different points in the pulse cycle. Methods: A healthy white male aged 19 years had 30 digitised images taken at three distinct points in the pulse cycle over a one hour period. A pulse synchronised ear clip trigger device was used to capture images at the desired point in the pulse cycle. Two trained graders measured the retinal vessel diameter of one large arteriole, one large venule, one small arteriole, and one small venule 10 times in each of these 30 images. Results: Within an image, variability was similar between graders, pulse point, and vessel type. Across images taken at the same point in the pulse period, the change from the minimum to maximum measurement was between 6% and 17% for arterioles and between 2% and 11% for venules. In addition, measurements of small vessels had greater changes than large vessels and no point in the pulse period was more variable than another. Ignoring pulse cycle increased variability across images in the large venule, but not in the other vessel types. Mixed effect models were fit for each of the vessel types to determine the greatest source of variability. Controlling for pulse point and grader, the largest source of variability for all four vessels measured was across images, accounting for more than 50% of the total variability. Conclusion: Measurements of large retinal venules is generally less variable than measurements of other retinal vessels. After controlling for pulse point and grader, the largest source of variation is across images. Understanding the components of variability in measuring retinal vessels is important as these techniques are applied in epidemiological studies.

PURPOSE:We compared the frequency and sequence of breast imaging and biopsy use for the diagnostic and preoperative workup of breast cancer according to breast magnetic resonance imaging (MRI) use among older women. MATERIALS AND METHODS:Using SEER-Medicare data from 2004 to 2010, we identified women with and without breast MRI as part of their diagnostic and preoperative breast cancer workup and measured the number and sequence of breast imaging and biopsy events per woman. RESULTS:A total of 10,766 (20%) women had an MRI in the diagnostic/preoperative period, 32,178 (60%) had mammogram and ultrasound, and 10,669 (20%) had mammography alone. MRI use increased across study years, tripling from 2005 to 2009 (9%–29%). Women with MRI had higher rates of breast imaging and biopsy compared with those with mammogram and ultrasound or those with mammography alone (5.8 vs. 4.1 vs. 2.8, respectively). There were 4254 unique sequences of breast events; the dominant patterns for women with MRI were an MRI occurring at the end of the care pathway. Among women receiving an MRI postdiagnosis, 26% had a subsequent biopsy compared with 51% receiving a subsequent biopsy in the subgroup without MRI. CONCLUSIONS:Older women who receive breast MRI undergo additional breast imaging and biopsy events. There is much variability in the diagnostic/preoperative work-up in older women, demonstrating the opportunity to increase standardization to optimize care for all women.