Pharmacovigilance using clinical notes.

With increasing adoption of electronic health records (EHRs), there is an opportunity to use the free-text portion of EHRs for pharmacovigilance. We present novel methods that annotate the unstructured clinical notes and transform them into a deidentified patient-feature matrix encoded using medical terminologies. We demonstrate the use of the resulting high-throughput data for detecting drug-adverse event associations and adverse events associated with drug-drug interactions. We show that these methods flag adverse events early (in most cases before an official alert), allow filtering of spurious signals by adjusting for potential confounding, and compile prevalence information. We argue that analyzing large volumes of free-text clinical notes enables drug safety surveillance using a yet untapped data source. Such data mining can be used for hypothesis generation and for rapid analysis of suspected adverse event risk.

Stochastic modeling of multiple ovulation and embryo transfer breeding schemes in small closed dairy cattle populations.

Genetic changes and genetic drift in three small closed dairy cattle populations were examined with a stochastic simulation model. Multiple ovulation and embryo transfer and AI techniques were simulated in three populations, two with 88 breeding females each and one with 352 breeding females. The selection goal was to maximize genetic improvement in milk yield. The reduction in genetic variation due to inbreeding and linkage disequilibrium was accounted for in the simulation. Strict restriction against inbred mating slowed genetic progress significantly in the small population but would not be consequential in the larger population. However, allowing inbred mating in the smaller population caused a rapid accumulation of inbreeding. Linkage disequilibrium was as important as inbreeding in reducing genetic variation. Genetic drift variance was much smaller in the larger population.

Relationship between dam's age at bull's birth and bull's genetic evaluation.

After accounting for year of birth of bulls, younger dams produced superior sons. Bulls' PD, parent average, and pedigree index milk decreased with increasing age of dams at bull's birth. This appears to be due to decrease in maternal grandsire's PD milk and dam's Cow Index milk with increase in age of dam. Younger dams have an advantage of potentially higher genetic merit due to genetic trend but have less information included in their evaluations. Bull's latest parent average and pedigree index overestimated latest PD milk. This overestimation was not different with age of dam at bull's birth, suggesting that the bias in predicting bulls' PD from eventual evaluations of dams chosen at a younger age is not different than for dams chosen at a later age. Data were for 2826 bulls sampled by four AI organizations and born between 1965 and 1981. The increase in PD milk of bulls was about 27 kg/yr, but the trend was larger (45 kg/yr) during the last 5 yr. Inclusion of dam's age did not improve prediction of bull's PD milk. Maternal grandsire's PD milk was the primary variable associated with dam's age that accounted for lower bull's PD milk, mainly because older dams tended to have sires of lower genetic merit.

Breakeven costs for embryo transfer in a commercial dairy herd.

Differences in Estimated Breeding Values expressed in dollars were compared by simulation of two, 100-cow, closed herds. One herd practiced normal intensity of female selection. The other herd generated various herd replacements by embryo transfer by varying 1) selection rate of embryo transfer dams and 2) numbers of daughters per dam from which embryos were transferred, while varying the merit of mates of embryo transfer dams. Estimated Breeding Value dollars were compounded each generation and regressed to remove age adjustments and added feed and health costs. Beginning values in both herds included a standard deviation of 55 Cow Index dollars, herd average of -23 Cow Index dollars, and a 120 Predicted Difference dollars for mates of dams not embryo transferred. Average merit of all sires used increased $12 per year. Herd calving rate (.70), proportion females (.5), calf loss (.15), and heifer survival rate (.83) were used. Breakeven cost per embryo transfer cow entering the milking herd was computed by Net Present Value analysis using a 10% discount rate over 10 and 20 yr. Breakeven cost or the maximum expense that would allow a 10% return on the expenditure ranged from $135 to $510 per surviving cow, $24 to $125 per transfer, $47 to $178 per pregnancy, and $81 to $357 per female calf born. As the number of replacements resulting from embryo transfer increased, breakeven cost per embryo transfer cow decreased due to diminishing return.

Selecting for lactation curve and milk yield in dairy cattle.

Knowledge of genetic relationships between characteristics of lactation curves and lactation yields is essential for joint selection for both. An equation, yt = atbexp(-ct), was chosen to depict individual lactation curves for 5,927 first lactations by Holsteins in 557 herds in Michigan Dairy Herd Improvement where yt is daily milk yield at day t in lactation, a is yield at time zero, b is ascent to peak, and c is decline after peak. Genetic correlations for 305-day milk yield with initial production (a), ascent to peak (b), descent after peak (c), and peak yield were -.37, .40, 0, and .91. From empirical results from applied selection indexes, selecting for both increase of ascent to peak and peak yield did not decrease 305-day milk substantially. Rankings of sires on these indexes were similar to their rankings on milk yield alone. Attempts to decrease peak yield and increase persistency decreased milk yield greatly.