Using milk mid-infrared spectroscopy to estimate cow-level nitrogen efficiency metrics.

Minimizing pollution from the dairy sector is paramount; one potential cause of such pollution is excess nitrogen. Nitrogen pollution contributes to a deterioration in water quality as well as an increase in both eutrophication and greenhouse gases. It is therefore essential to minimize the loss of nitrogen from the sector, including excretion from the cow. Breeding programs are one potential strategy to improve the efficiency with which nitrogen is used by dairy cows but relies on routine access to individual cow information on how efficiently each cows uses the nitrogen it ingests. A total of 3,497 test-day records for individual cow nitrogen efficiency metrics along with milk yield and the associated milk spectra were used to investigate the ability of milk infrared spectral data to predict these nitrogen traits; both traditional partial least squares regression and neural networks were used in the prediction process. The data originated from 4 farms across 11 years. The nitrogen traits investigated were nitrogen intake, nitrogen use efficiency, and nitrogen balance. Both nitrogen use efficiency and nitrogen balance were calculated considering nitrogen intake, nitrogen in milk, nitrogen in the conceptus, nitrogen used for the growth, nitrogen stored in the reserves, and nitrogen mobilized from the reserves. Irrespective of the nitrogen-related trait being investigated, the best prediction from 4-fold cross-validation were achieved using neural networks that considered both the morning and evening milk spectra along with milk yield, parity, and days in milk in the prediction process. The coefficient of determination in the cross-validation was 0.61, 0.74, and 0.58 for nitrogen intake, nitrogen use efficiency, and nitrogen balance, respectively. In a separate series of validation approaches, the calibration and validation was stratified by herd (n = 4) and separately by year. For these scenarios, partial least squares regression generated more accurate predictions compared with neural networks; the coefficient of determination was always lower than 0.29 and 0.60 when validation was stratified by herd and year, respectively. Therefore, if the variability of the data being predicted in the validation data sets is similar to that in the data used to develop the predictions, then nitrogen-related traits can be predicted with reasonable accuracy. In contrast, where the variability of the data that exists in the validation data set is poorly represented in the calibration data set, then poor predictions will ensue.

Genetic covariance components for measures of nitrogen utilization in grazing dairy cows.

Improved nitrogen utilization of dairy production systems should improve not only the economic output of the systems but also the environmental metrics. One strategy to improve efficiency is through breeding programs. Improving a trait through breeding is conditional on the presence of exploitable genetic variability. Using a database of 1,291 deeply phenotyped grazing dairy cows, the genetic variability for 2 definitions of nitrogen utilization was studied: nitrogen use efficiency (i.e., nitrogen output in milk and meat divided by nitrogen available) and nitrogen balance (i.e., nitrogen available less nitrogen output in milk and meat). Variance components for both variables were estimated using animal repeatability linear mixed models. Genetic variability was detected for both nitrogen utilization metrics, even though their heritability estimates were low (<0.10). Validation of genetic evaluations revealed that animals divergent for nitrogen use efficiency or nitrogen balance indeed differed phenotypically, further demonstrating that breeding for improved nitrogen efficiency should result in a shift in the population mean toward better efficiency. Nitrogen use efficiency and nitrogen balance were not genetically correlated with each other (<|0.28|), and neither metric was correlated with milk urea nitrogen (<|0.12|). Nitrogen balance was unfavorably correlated with milk yield, showing the importance of including the nitrogen utilization metrics in a breeding index to improve nitrogen utilization without negatively impacting milk yield. In conclusion, improvement of nitrogen utilization through breeding is possible, even if more nitrogen utilization phenotypic data need to be collected to improve the selection accuracy considering the low heritability estimates.

The association between calf birth weight and the postcalving performance of its dairy dam in the absence of dystocia.

The objective of the study was to quantify the association between the birth weight of a calf and the subsequent performance of its dairy dam in the absence of any recorded calving assistance. A total of 11,592 lactation records from 4,549 spring-calving dairy cows were used. The association between a series of quantitative cow performance metrics (dependent variable) and calf birth weight (independent variable) was determined using linear mixed models; logistic regression was used where the dependent variable was binary. Nuisance factors in the models were calf sex, heterosis coefficient of both the cow and calf, dry period length immediately before the birth of the calf, cow age at calving relative to the median cow age per parity, breed proportion of the cow, cow live weight between 100 and 200 d of lactation relative to the mean cow weight per parity, and contemporary group. Calf birth weight was included in the model as either a continuous or a categorical variable. Primiparous and multiparous cows were analyzed separately. Mean (SD) calf birth weight was 36.2 (6.8) kg. In primiparous cows, calf birth weight was associated with milk yield in the first 60 d of lactation, calving to first service interval, calving body weight (BW), and both nadir BW and body condition score (BCS). In multiparous cows, calf birth weight was associated with total milk, fat, and protein yield in the first 60 and 305 d of lactation, peak milk yield, total milk solids, both calving and nadir BW, and BCS loss from calving to nadir. Relative to primiparous cows that gave birth to calves weighing 34 to 37 kg (i.e., population mean), their contemporaries who gave birth to calves that weighed 15 to 29 kg produced 9.82 kg more milk in the first 60 d of lactation, had a 2-d shorter interval to first service, and were 8.08 kg and 5.51 kg lighter at calving and nadir BW, respectively; the former was also 0.05 units lower in BCS (5-point scale, 1 = emaciated and 5 = obese) at nadir. Relative to multiparous cows that gave birth to calves that were 34 to 37 kg birth weight, multiparous cows that gave birth to calves that were 15 to 29 kg yielded 59.63 kg, 2.44 kg, and 1.76 kg less milk, fat, and protein, respectively, in the first 60 d of lactation; produced 17.69 kg less milk solids throughout the 305-d lactation; and were also 10.49 kg lighter at nadir and lost 0.01 units more BCS to nadir. In a separate series of analyses, sire breed was added to the model as a fixed effect with and without calf birth weight. When calf birth weight was not adjusted for, 60-d milk yield for multiparous cows who gave birth to calves sired by a traditional beef breed (i.e., Angus, Hereford) produced 59.63 kg more milk than multiparous cows who gave birth to calves sired by a Holstein-Friesian. Hence, calf birth weight is associated with some subsequent dam performance measures; however, where associations do exist, the effect is biologically small.

Predicting methane emissions of individual grazing dairy cows from spectral analyses of their milk samples.

Data on the enteric methane emissions of individual cows are useful not just in assisting management decisions and calculating herd inventories but also as inputs for animal genetic evaluations. Data generation for many animal characteristics, including enteric methane emissions, can be expensive and time consuming, so being able to extract as much information as possible from available samples or data sources is worthy of investigation. The objective of the present study was to attempt to predict individual cow methane emissions from the information contained within milk samples, specifically the spectrum of light transmittance across different wavelengths of the mid-infrared (MIR) region of the electromagnetic spectrum. A total of 93,888 individual spot measures of methane (i.e., individual samples of an animal's breath when using the GreenFeed technology) from 384 lactations on 277 grazing dairy cows were collapsed into weekly averages expressed as grams per day; each weekly average coincided with a MIR spectral analysis of a morning or evening individual cow milk sample. Associations between the spectra and enteric methane measures were performed separately using partial least squares regression or neural networks with different tuning parameters evaluated. Several alternative definitions of the enteric methane phenotype (i.e., average enteric methane in the 6 d preceding or 6 d following taking the milk sample or the average of the 6 d before and after the milk sample, all of which also included the enteric methane emitted on the day of milk sampling), the candidate model features (e.g., milk yield, milk composition, and milk MIR) as well as validation strategy (i.e., cross-validation or leave-one-experimental treatment-out) were evaluated. Irrespective of the validation method, the prediction accuracy was best when the average of the milk MIR from the morning and evening milk sample was used and the prediction model was developed using neural networks; concurrently including milk yield and days in milk in the prediction model generated superior predictions relative to just the spectral information alone. Furthermore, prediction accuracy was best when the enteric methane phenotype was the average of at least 20 methane spot measures across a 6-d period flanking each side of the milk sample with associated spectral data. Based on the strategy that achieved the best accuracy of prediction, the correlation between the actual and predicted daily methane emissions when based on 4-fold cross-validation varied per validation stratum from 0.68 to 0.75; the corresponding range when validated on each of the 8 different experimental treatments focusing on alternative pasture grazing systems represented in the dataset varied from 0.55 to 0.71. The root mean square error of prediction across the 4-folds of cross-validation was 37.46 g/d, whereas the root mean square error averaged across all folds of leave-one-treatment-out was 37.50 g/d. Results suggest that even with the likely measurement errors contained within the MIR spectrum and gold standard enteric methane phenotype, enteric methane can be reasonably well predicted from the infrared spectrum of milk samples. What is yet to be established, however, is whether (a) genetic variation exists in this predicted enteric methane phenotype and (b) selection on estimates of genetic merit for this phenotype translate to actual phenotypic differences in enteric methane emissions.

Impact on prime animal beef merit from breeding solely for lighter dairy cows.

As the proportion of prime carcasses originating from dairy herds increases, the focus is shifting to the beef merit of the progeny from dairy herds. Several dairy cow total merit indexes include a negative weight on measures of cow size. However, there is a lack of knowledge on the impact of genetic selection, solely for lighter or smaller-sized dairy cows, on the beef performance of their progeny. Therefore, the objective of this study was to quantify the genetic correlations among cow size traits (i.e., cow body weight (BW), cow carcass weight (CW)), cow body condition score (BCS), cow carcass conformation (CC), and cow carcass fat cover (CF), as well as the correlations between these cow traits and a series of beef performance slaughter-related traits (i.e., CW, CC, CF, and age at slaughter (AS)) in their progeny. After data editing, there were 52,950 cow BW and BCS records, along with 57,509 cow carcass traits (i.e., CW, CC, and CF); carcass records from 346,350 prime animals along with AS records from 316,073 prime animals were also used. Heritability estimates ranged from moderate to high (0.18 to 0.62) for all cow and prime animal traits. The same carcass trait in cows and prime animals were strongly genetically correlated with each other (0.76 to 0.85), implying that they are influenced by very similar genomic variants. Selecting exclusively for cows with higher BCS (i.e., fatter) will, on average, produce more conformed prime animals carcasses, owing to a moderate genetic correlation (0.30) between both traits. Genetic correlations revealed that selecting exclusively for lighter BW or CW cows will, on average, result in lighter prime animal carcasses of poor CC, while also delaying slaughter age. Nonetheless, selective breeding through total merit indexes should be successful in breeding for smaller dairy cows, and desirable prime animal carcass traits concurrently, because of the non-unity genetic correlations between the cow and prime animal traits; this will help to achieve a more ethical, environmentally sustainable, and economically viable dairy-beef industry.

Double pulsed field gradient diffusion MRI to assess skeletal muscle microstructure.

PURPOSE: Preliminary study to determine whether double pulsed field gradient (PFG) diffusion MRI is sensitive to key features of muscle microstructure related to function. METHODS: The restricted diffusion profile of molecules in models of muscle microstructure derived from histology were systematically simulated using a numerical simulation approach. Diffusion tensor subspace imaging analysis of the diffusion signal was performed, and spherical anisotropy (SA) was calculated for each model. Linear regression was used to determine the predictive capacity of SA on the fiber area, fiber diameter, and surface area to volume ratio of the models. Additionally, a rat model of muscle hypertrophy was scanned using a single PFG and a double PFG pulse sequence, and the restricted diffusion measurements were compared with histological measurements of microstructure. RESULTS: Excellent agreement between SA and muscle fiber area (r2 = 0.71; p < 0.0001), fiber diameter (r2 = 0.83; p < 0.0001), and surface area to volume ratio (r2 = 0.97; p < 0.0001) in simulated models was found. In a scanned rat leg, the distribution of these microstructural features measured from histology was broad and demonstrated that there is a wide variance in the microstructural features observed, similar to the SA distributions. However, the distribution of fractional anisotropy measurements in the same tissue was narrow. CONCLUSIONS: This study demonstrates that SA-a scalar value from diffusion tensor subspace imaging analysis-is highly sensitive to muscle microstructural features predictive of function. Furthermore, these techniques and analysis tools can be translated to real experiments in skeletal muscle. The increased dynamic range of SA compared with fractional anisotropy in the same tissue suggests increased sensitivity to detecting changes in tissue microstructure.

Mean breed performance of the progeny from beef-on-dairy matings.

Gains through breeding can be achieved through a combination of both between-breed and within-breed selection. Two suites of traits of particular interest to dairy producers when selecting beef bulls for mating to dairy females are calving-related attributes and the expected value of the subsequent calf, the latter usually being a function of expected carcass value. Estimated breed effects can be informative, particularly in the absence of across-breed genetic evaluations. The objective of the present study was to use a large national database of the progeny from beef-on-dairy matings to estimate the mean breed effects of the used beef sires. Calving performance (i.e., gestation length, calving difficulty score, and perinatal morality) as well as calf value were investigated; a series of slaughter-related traits (i.e., carcass metrics and age at slaughter) of the prime progeny were also investigated. Phenotypic data on up to 977,037 progeny for calving performance, 79,903 for calf price and 103,175 for carcass traits (including dairy × dairy progeny for comparative purposes) were used; sire breeds represented were Holstein-Friesian, Angus, Aubrac, Belgian Blue, Charolais, Hereford, Limousin, Salers, and Simmental. Large interbreed differences existed. The mean gestation length of male calves from beef sires varied from 282.3 d (Angus) to 287.4 d (Limousin) which were all longer than the mean of 280.9 d for Holstein-Friesian sired male calves. Relative to a Holstein-Friesian sire, the odds of dystocia varied from 1.43 (Angus) to 4.77 (Belgian Blue) but, once adjusted for both the estimated maternal genetic merit of the dam and direct genetic merit of the calf for calving difficulty, the range in odds ratios shrunk. A difference of €125.4 existed in calf sale price between the progeny of the different beef breeds investigated which represented over twice the residual standard deviation in calf price within the day of sale-Angus was the cheapest while Charolais calves were, on average, the most expensive calves. Mean carcass weight of steers, not adjusted for age at slaughter or carcass fat, varied from 327.1 kg (Angus) to 363.2 kg (Belgian Blue) for the beef breeds with the mean carcass weight of Holstein-Friesian steer progeny being 322.4 kg. Belgian Blues had, on average, the best carcass conformation with the Herefords and Angus having the worst of all beef breeds. Angus and Hereford steers were slaughtered the youngest of all beef breeds but just 9 d younger than the average of all other beef breeds yet 24 d younger than Holstein-Friesian sired progeny. Clear breed differences in calving and carcass performance exist among beef breeds mated to dairy females. Those breeds excelling in calving performance were not necessarily the best for carcass merit.

Usefulness of mid-infrared spectroscopy as a tool to estimate body condition score change from milk samples in intensively fed dairy cows.

Directly measuring individual cow energy balance is not trivial. Other traits such as body condition score (BCS) and BCS change (ΔBCS) can, however, be used as an indicator of cow energy status. Body condition score is a metric used worldwide to estimate cow body reserves, but the estimation of ΔBCS was, until now, conditional on the availability of multiple BCS assessments. The aim of the present study was to estimate ΔBCS from milk mid-infrared (MIR) spectra and days in milk (DIM) in intensively fed dairy cows using statistical prediction methods. Daily BCS was interpolated from cubic splines fitted through the BCS records and daily ΔBCS was calculated from these splines. The ΔBCS records were merged with milk MIR spectra recorded on the same week. The dataset comprised 37,077 ΔBCS phenotypes across 9,403 lactations from 6,988 cows in 151 herds based in Quebec, Canada. Partial least squares regression (PLSR) and a neural network (NN) were then used to estimate ΔBCS from (1) MIR spectra only, (2) DIM only, or (3) MIR spectra and DIM together. The ΔBCS data in both the first 120 and 305 DIM of lactation were used to develop the estimates. Daily ΔBCS had a standard deviation of 4.40 × 10-3 BCS units in the 120-d dataset and of 3.63 × 10-3 BCS units in the 305-d dataset. A 4-fold cross-validation was used to calibrate and test the prediction equations. External validation was also conducted using more recent years of data. Irrespective of whether based on the first 120 or 305 DIM, or when MIR spectra only, DIM only or MIR spectra and DIM were jointly used as prediction variables, NN produced the lowest root mean square error (RMSE) of cross-validation (1.81 × 10-3 BCS units and 1.51 × 10-3 BCS units, respectively, using the 120-d and 305-d dataset). Relative to predictions for the entire 305 DIM, the RMSE of cross-validation was 15.4% and 1.5% lower in the first 120 DIM when using PLSR and NN, respectively. Predictions from DIM only were more accurate than those using just MIR spectra data but, irrespective of the dataset and of the prediction model used, combining DIM information with MIR spectral data as prediction variables reduced the RMSE compared with the inclusion of DIM alone, albeit the benefit was small (the RMSE from cross-validation reduced by up to 5.5% when DIM and spectral data were jointly used as model features instead of DIM only). However, when predicting extreme ΔBCS records, the MIR spectral data were more informative than DIM. Model performance when predicting ΔBCS records in future years was similar to that from cross-validation demonstrating the ability of MIR spectra of milk and DIM combined to estimate ΔBCS, particularly in early lactation. This can be used to routinely generate estimates of ΔBCS to aid in day-to-day individual cow management.

Estimation of body condition score change in dairy cows in a seasonal calving pasture-based system using routinely available milk mid-infrared spectra and machine learning techniques.

Body condition score (BCS) is a subjective estimate of body reserves in cows. Body condition score and its change in early lactation have been associated with cow fertility and health. The aim of the present study was to estimate change in BCS (ΔBCS) using mid-infrared spectra of the milk, with a particular focus on estimating ΔBCS in cows losing BCS at the fastest rate (i.e., the cows most of interest to the producer). A total of 73,193 BCS records (scale 1 to 5) from 6,572 cows were recorded. Daily BCS was interpolated from cubic splines fitted through the BCS records, and subsequently used to calculate daily ΔBCS. Body condition score change records were merged with milk mid-infrared spectra recorded on the same week. Both morning (a.m.) and evening (p.m.) spectra were available. Two different statistical methods were used to estimate ΔBCS: partial least squares regression and a neural network (NN). Several combinations of variables were included as model features, such as days in milk (DIM) only, a.m. spectra only and DIM, p.m. spectra only and DIM, and a.m. and p.m. spectra as well as DIM. The data used to estimate ΔBCS were either based on the first 120 DIM or all 305 DIM. Daily ΔBCS had a standard deviation of 1.65 × 10-3 BCS units in the 305 DIM data set and of 1.98 × 10-3 BCS units in the 120 DIM data set. Each data set was divided into 4 sub-data sets, 3 of which were used for training the prediction model and the fourth to test it. This process was repeated until all the sub-data sets were considered as the test data set once. Using all 305 DIM, the lowest root mean square error of validation (RMSEV; 0.96 × 10-3 BCS units) and the strongest correlation between actual and estimated ΔBCS (0.82) was achieved with NN using a.m. and p.m. spectra and DIM. Using the 120 DIM data, the lowest RMSEV (0.98 × 10-3 BCS units) and the strongest correlation between actual and estimated ΔBCS (0.87) was achieved with NN using DIM and either a.m. spectra only or a.m. and p.m. spectra together. The RMSEV for records in the lowest 2.5% ΔBCS percentile per DIM in early lactation was reduced up to a maximum of 13% when spectra and DIM were both considered in the model compared with a model that considered just DIM. The performance of the NN using DIM and a.m. spectra only with the 120 DIM data was robust across different strata of farm, parity, year of sampling, and breed. Results from the present study demonstrate the ability of mid-infrared spectra of milk coupled with machine learning techniques to estimate ΔBCS; specifically, the inclusion of spectral data reduced the RMSEV over and above using DIM alone, particularly for cows losing BCS at the fastest rate. This approach can be used to routinely generate estimates of ΔBCS that can subsequently be used for farm decisions.

Early detection of subclinical mastitis in lactating dairy cows using cow-level features.

Subclinical mastitis in cows affects their health, well-being, longevity, and performance, leading to reduced productivity and profit. Early prediction of subclinical mastitis can enable dairy farmers to perform interventions to mitigate its effect. The present study investigated how well predictive models built using machine learning techniques can detect subclinical mastitis up to 7 d before its occurrence. The data set used consisted of 1,346,207 milk-day (i.e., a day when milk was collected on both morning and evening) records spanning 9 yr from 2,389 cows producing on 7 Irish research farms. Individual cow composite milk yield and maximum milk flow were available twice daily, whereas milk composition (i.e., fat, lactose, protein) and somatic cell count (SCC) were collected once per week. Other features describing parity, calving dates, predicted transmitting ability for SCC, body weight, and history of subclinical mastitis were also available. The results of the study showed that a gradient boosting machine model trained to predict the onset of subclinical mastitis 7 d before a subclinical case occurs achieved a sensitivity and specificity of 69.45 and 95.64%, respectively. Reduced data collection frequency, where milk composition and SCC were recorded only every 15, 30, 45, and 60 d was simulated by masking data, to reflect the frequency of recording of this data on commercial dairy farms in Ireland. The sensitivity and specificity scores reduced as recording frequency reduced with respective scores of 66.93 and 80.43% when milk composition and SCC were recorded just every 60 d. Results demonstrate that models built on data that could be recorded routinely available on commercial dairy farms, can achieve useful predictive ability of subclinical mastitis even with reduced frequency of milk composition and SCC recording.

Cow-level factors associated with nitrogen utilization in grazing dairy cows using a cross-sectional analysis of a large database.

Reducing nitrogen pollution while maintaining milk production is a major challenge of dairy production. One of the keys to delivering on this challenge is to improve the efficiency of how dairy cows use nitrogen. Thus, estimating the nitrogen utilization of lactating grazing dairy cows and exploring the association between animal factors and productivity with nitrogen utilization are the first steps to understanding the nitrogen utilization complex in dairy cows. Nitrogen utilization metrics were derived from milk and body weight records from 1,291 grazing dairy cows of multiple breeds and crossbreeds; all cows had sporadic information on nitrogen intake concurrent with information on nitrogen sinks (and other nitrogen sources, such as body tissue mobilization). Several nitrogen utilization metrics were investigated, including nitrogen use efficiency (nitrogen output as products such as milk and meat divided by nitrogen intake) and nitrogen excreted (nitrogen intake less the nitrogen output as products such as milk and meat). In the present study, a primiparous Holstein-Friesian used, on average, 20.6% of the nitrogen it ate, excreting the surplus as feces and urine, representing 402 g of nitrogen per day. Intercow variability existed, with a between-cow standard deviation of 0.0094 for nitrogen use efficiency and 24 g of nitrogen per day for nitrogen excretion. As lactation progressed, nitrogen use efficiency declined and nitrogen excretion increased. Nevertheless, nitrogen use efficiency improved (i.e., decreased) from first to second parity, even though it did not improve from second to third parity or greater. Furthermore, nitrogen excretion continued to increase from first to third parity or greater. Nitrogen use efficiency and nitrogen excretion were negatively correlated (-0.56 to -0.40), signifying that dairy cows who partition more of the ingested nitrogen into products such as milk and meat, on average, also excrete less nitrogen. Milk urea nitrogen was, at best, weakly correlated with nitrogen use efficiency and nitrogen excretion; the correlations were between -0.01 and 0.06. In conclusion, several cow-level factors such as parity, stage of lactation, and breed were associated with the range of different nitrogen efficiency metrics investigated; moreover, even after accounting for such effects, 4.8% to 6.3% of the remaining variation in the nitrogen use efficiency and nitrogen balance metrics were attributable to intercow differences.

Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n = 72) and corresponding controls (n = 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n = 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. RESULTS: In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. CONCLUSIONS: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

Re-assessing the importance of linear type traits in predicting genetic merit for survival in an aging Holstein-Friesian dairy cow population.

The cumulative improvement achieved in the genetic merit for reproductive performance in dairy populations will likely improve dairy cow longevity; therefore, it is time to reassess whether linear type traits are still suitable predictors of survival in an aging dairy cow population. The objective of the present study was therefore to estimate the genetic correlations between linear type traits and survival from one parity to the next and, in doing so, evaluate if those genetic correlations change with advancing parity. After edits, 152,894 lactation survival records (first to ninth parity) were available from 52,447 Holstein-Friesian cows, along with linear type trait records from 52,121 Holstein-Friesian cows. A series of bivariate random regression models were used to estimate the genetic covariances between survival in different parities and each linear type trait. Heritability estimates for survival per parity ranged from 0.02 (SE = 0.004; first parity) to 0.05 (SE = 0.01; ninth parity). Pairwise genetic correlations between survival among different parities varied from 0.42 (first and ninth parity) to 1.00 (eighth to ninth parity), with the strength of these genetic correlations being inversely related to the interval between the compared parities. The genetic correlations between survival and the individual linear type traits varied across parities for 9 of the 20 linear type traits examined, but the correlations with only 3 of these linear type traits strengthened as the cows aged; these 3 traits were rear udder height, teat length, and udder depth. Given that linear type traits are frequently scored in first parity and are genetically correlated with survival in older parities, they may be suitable early predictors of survival, especially for later parity cows. Additionally, the direction of the genetic correlations between survival and rear udder height, teat length, and udder depth did not change between parities; hence, selection for survival in older parities using these linear type traits should not hinder genetic improvement for survival in younger parities.

Exploiting genetic variability in the trajectory of lactation yield and somatic cell score with each progressing parity.

The inclusion of reproductive performance in dairy cow breeding schemes has resulted in a cumulative improvement in genetic merit for reproductive performance; this improvement should manifest in longer productive lives through a reduced requirement for involuntary culling. Nonetheless, the average length of dairy cow productive life has not changed in most populations, suggesting that risk factors for culling, especially in older cows, are possibly more associated with lower yield or high somatic cell score (SCS) than compromised reproductive performance. The objective of the present study was to understand the dynamics of lactation yields and SCS in dairy cows across parities and, in doing so, quantify the potential to alter this trajectory through breeding. After edits, 3,470,520 305-d milk, fat, and protein yields, as well as milk fat and protein percentage and somatic cell count records from 1,162,473 dairy cows were available for analysis. Random regression animal models were used to identify the parity in which individual cows reached their maximum lactation yields, and highest average milk composition and SCS; also estimated from these models were the (co)variance components for yield, composition, and SCS per parity across parities. Estimated breeding values for all traits per parity were calculated for cows reaching ≥fifth parity. Of the cows included in the analyses, 91.0%, 92.2%, and 83.4% reached maximum milk, fat, and protein yield in fifth parity, respectively. Conversely, 95.9% of cows reached their highest average fat percentage in first parity and 62.9% of cows reached their highest average protein percentage in third parity. In contrast to both milk yield and composition traits, 98.4% of cows reached their highest average SCS in eighth parity. Individual parity estimates of heritability for milk yield traits, milk composition, and SCS ranged from 0.28 to 0.44, 0.47 to 0.69, and 0.13 to 0.23, respectively. The strength of the genetic correlations per trait among parities was inversely related to the interval between the parities compared; the weakest genetic correlation was 0.67 (standard error = 0.02) between milk yield in parities 1 and 8. Eigenvalues and eigenfunctions of the additive genetic covariance matrices for all investigated traits revealed potential to alter the trajectory of parity profiles for milk yield, milk composition, and SCS. This was further demonstrated when evaluating the trajectories of animal estimated breeding values per parity.

Are subjectively scored linear type traits suitable predictors of the genetic merit for feed intake in grazing Holstein-Friesian dairy cows?

Measuring dry matter intake (DMI) in grazing dairy cows using currently available techniques is invasive, time consuming, and expensive. An alternative to directly measuring DMI for use in genetic evaluations is to identify a set of readily available animal features that can be used in a multitrait genetic evaluation for DMI. The objectives of the present study were thus to estimate the genetic correlations between readily available body-related linear type traits and DMI in grazing lactating Holstein-Friesian cows, but importantly also estimate the partial genetic correlations between these linear traits and DMI, after adjusting for differences in genetic merit for body weight. Also of interest was whether the predictive ability derived from the estimated genetic correlations materialized upon validation. After edits, a total of 8,055 test-day records of DMI, body weight, and milk yield from 1,331 Holstein-Friesian cows were available, as were chest width, body depth, and stature from 47,141 first lactation Holstein-Friesian cows. In addition to considering the routinely recorded linear type traits individually, novel composite traits were defined as the product of the linear type traits as an approximation of rumen volume. All linear type traits were moderately heritable, with heritability estimates ranging from 0.27 (standard error = 0.14) to 0.49 (standard error = 0.15); furthermore, all linear type traits were genetically correlated (0.29 to 0.63, standard error 0.14 to 0.12) with DMI. The genetic correlations between the individual linear type traits and DMI, when adjusted for genetic differences in body weight, varied from -0.51 (stature) to 0.48 (chest width). These genetic correlations between DMI and linear type traits suggest linear type traits may be useful predictors of DMI, even when body weight information is available. Nonetheless, estimated genetic merit of DMI derived from a multitrait genetic evaluation of linear type traits did not correlate strongly with actual DMI in a set of validation animals; the benefit was even less if body weight data were also available.

Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.

BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Physiologic and psychosocial changes of the menopause transition in US Latinas: a narrative review.

Latinos comprise the fastest-growing minority group in the USA, with Hispanic women (Latinas) constituting 17% of women aged 45-54 years. The menopause transition (MT) is associated with many physiological, behavioral, and psychosocial changes that can affect disease risk in women. While several epidemiologic investigations have enhanced our understanding of the MT, to date, menopause research has mostly focused on non-Latina White women. As a consequence, there is a dearth of information on strategies for managing menopause-related issues in Latinas and important factors to consider to provide culturally appropriate care and promote lifestyles that may reduce adverse health outcomes. This narrative review summarizes existing evidence of the MT in Latinas, with a focus on hormonal alterations, menopausal symptoms, mental health, cognition, and cardiometabolic health. The clinical and research implications of the current literature will also be discussed.

Concordance rate in cattle and sheep between genotypes differing in Illumina GenCall quality score.

Proper quality control of data prior to downstream analyses is fundamental to ensure integrity of results; quality control of genomic data is no exception. While many metrics of quality control of genomic data exist, the objective of the present study was to quantify the genotype and allele concordance rate between called single nucleotide polymorphism (SNP) genotypes differing in GenCall (GC) score; the GC score is a confidence measure assigned to each Illumina genotype call. This objective was achieved using Illumina beadchip genotype data from 771 cattle (12 428 767 genotypes in total post-editing) and 80 sheep (1 557 360 SNPs genotypes in total post-editing) each genotyped in duplicate. The called genotype with the lowest associated GC score was compared to the genotype called for the same SNP in the same duplicated animal sample but with a GC score of >0.90 (assumed to represent the true genotype). The mean genotype concordance rate for a GC score of <0.300, 0.300-0.549, and ≥0.550 in the cattle (sheep in parenthesis) was 0.9467 (0.9864), 0.9707 (0.9953), and 0.9994 (0.99997) respectively; the respective allele concordance rate was 0.9730 (0.9930), 0.9849 (0.9976), and 0.9997 (0.99998). Hence, concordance eroded as the GC score of the called genotype reduced, albeit the impact was not dramatic and was not very noticeable until a GC score of <0.55. Moreover, the impact was greater and more consistent in the cattle population than in the sheep population. Furthermore, an impact of GC score on genotype concordance rate existed even for the same SNP GenTrain value; the GenTrain value is a statistical score that depicts the shape of the genotype clusters and the relative distance between the called genotype clusters.

Increasing uptake of National Health Service Health Checks in primary care: a pragmatic randomized controlled trial of enhanced invitation letters in Northamptonshire, England.

BACKGROUND: Uptake of NHS Health Checks (NHSHCs) is sub-optimal. This study aimed to increase their uptake using behaviourally informed invitation letters. METHOD: Patients registered with 6 general practices in Northamptonshire, England who were eligible for an NHSHC between 10 February 2014 and 31 January 2015 were randomized monthly, using a random number generator, to three trial arms: control (standard invitation), sunk costs (resources already allocated) and counterargument (against common barriers to attendance). The outcome measure was uptake of NHSHC by 12 weeks after 31 January. RESULTS: In total, 6331 patients were randomized. After exclusions, due to ineligibility for the NHSHC, data were analysed for N = 6313 patients: N = 2123 control; N = 2085 counterargument; N = 2105 sunk costs. Overall, 2364 (37.45%) patients attended an NHSHC. Both intervention letters increased uptake compared to control, by 5.46% using counterargument (adjusted odds ratio (AOR) 1.32, CI 1.162-1.51, p < 0.001) and 4.33% using sunk costs (AOR 1.246, CI 1.10-1.42, p < 0.001), with no significant difference between the two. CONCLUSION: Behaviourally informed invitation letters, containing sunk costs or counterargument messages, can improve the uptake of NHSHCs. The trial was registered with the International Standard Randomised Controlled Trial Registration Number Scheme (ISRCTN57110614).

Invited review: Beef-on-dairy-The generation of crossbred beef × dairy cattle.

Because a growing proportion of the beef output in many countries originates from dairy herds, the most critical decisions about the genetic merit of most carcasses harvested are being made by dairy producers. Interest in the generation of more valuable calves from dairy females is intensifying, and the most likely vehicle is the use of appropriately selected beef bulls for mating to the dairy females. This is especially true given the growing potential to undertake more beef × dairy matings as herd metrics improve (e.g., reproductive performance) and technological advances are more widely adopted (e.g., sexed semen). Clear breed differences (among beef breeds but also compared with dairy breeds) exist for a whole plethora of performance traits, but considerable within-breed variability has also been demonstrated. Although such variability has implications for the choice of bull to mate to dairy females, the fact that dairy females themselves exhibit such genetic variability implies that "one size fits all" may not be appropriate for bull selection. Although differences in a whole series of key performance indicators have been documented between beef and beef-on-dairy animals, of particular note is the reported lower environmental hoofprint associated with beef-on-dairy production systems if the environmental overhead of the mature cow is attributed to the milk she eventually produces. Despite the known contribution of beef (i.e., both surplus calves and cull cows) to the overall gross output of most dairy herds globally, and the fact that each dairy female contributes half her genetic merit to her progeny, proxies for meat yield (i.e., veal or beef) are not directly considered in the vast majority of dairy cow breeding objectives. Breeding objectives to identify beef bulls suitable for dairy production systems are now being developed and validated, demonstrating the financial benefit of using such breeding objectives over and above a focus on dairy bulls or easy-calving, short-gestation beef bulls. When this approach is complemented by management-based decision-support tools, considerable potential exists to improve the profitability and sustainability of modern dairy production systems by exploiting beef-on-dairy breeding strategies using the most appropriate beef bulls.