Symposium review: An abundance of replacement heifers: What is the economic impact of raising more than are needed?

Historically, most dairy producers raised every heifer born, to ensure a supply of future replacements. However, advancements in transition and reproductive management, coupled with widespread use of sex-sorted semen in dairy heifers and cows, have led to an oversupply of dairy replacement heifers in the United States. With current market values for prepartum heifers at $1,300 and estimated raising costs ranging from $1,700 to $2,400, dairies that continue to produce quantities of heifers in excess of anticipated needs with plans of selling the extras on the open market are likely to experience significant economic loss. Adult cow herd turnover is the key driver behind the number of heifers needed to calve; however, mortality, disease, fertility, and elective culling losses throughout the heifer-raising period determine the total number of heifers that must be retained and raised to meet anticipated needs. A convenience sample of 50 US dairy herds revealed an average heifer inventory of 102% of total milking and dry cows. In this data set, the mean annualized adult herd turnover was 39%. With a mean stillbirth risk of 5.7% in calving heifers, a culling risk of 10.2% by 13 mo of age, a reproductive failure risk of 6.8% in breeding heifers, and an additional culling risk of 6.4% in pregnant heifers, only 74% of calving events with a heifer birth yielded a heifer that entered the lactating herd. Much of this heifer removal was elective, and making the correct culling decisions at the appropriate time yields the best return for the herd. To demonstrate how a herd might approach the elective culling issue, a records-based exercise with 2 large Holstein herds was performed to estimate the cost versus benefit of 3 different elective culling approaches, using a combination of genetic potential and growth performance as the selective criteria. However, the culling of heifers results in economic losses, because the revenue received is less than the cost incurred during raising. Selective culling of heifers soon after weaning yielded the best results in both herds, but despite the predicted improvement in lactation performance of the retained group, the cost associated with removal was greater than the benefit predicted. Culling a group early and then culling a second group just before calving yielded the largest loss. Moving forward, herds should breed more carefully to produce better-quality heifers from more superior dams and sires and consider the use of beef semen in inferior animals. However, to reduce the risk of not producing an adequate supply of replacement heifers, dairies should add an additional buffer to their anticipated needs. Using the assumptions within this project, having 10% extra calving events with a heifer birth would allow the annualized adult herd turnover to rise from 39 to 43% in case economic conditions or health status of the herd should change. If these heifers are not needed, the selection criteria outline could be used to help identify more valuable animals to retain.

Do biological and management reasons for a short or long dry period induce the same effects on dairy cattle productivity?

The dry period is a well-established factor that determines lactation success. A retrospective observational study used 32,182 lactations from 16 farms to determine whether management versus biological reasons for deviations from the targeted 60-d dry period have the same associations with subsequent lactation performance. Herd inclusion criteria were Holstein cows, herd size ≥900 cows, breeding by artificial insemination, and (minimally) bimonthly milk testing. Dry period length (DPL) and gestation length (GL) were each categorized as short [>1 standard deviation (SD) below mean within herd; means 45 d DPL, 269 d GL] or long (>1 SD above mean within herd; means 73 d DPL, 284 d GL) and combined to generate the following 7 study groups: short DPL, short GL (SDSG, n = 2,123); short DPL, average GL (SDAG, n = 1,418); average DPL, short GL (ADSG, n = 1,759); average DPL, average GL (ADAG, n = 19,265); average DPL, long GL (ADLG, n = 3,325); long DPL, average GL (LDAG, n = 2,573); and long DPL, long GL (LDLG, n = 1,719). Responses evaluated included milk and component yields at first test and over the whole lactation, days to first service, first service conception risk, days open, and herd retention through 60 and 365 d postpartum. Continuous data were analyzed by mixed models and time to event data by Cox proportional hazard models, both accounting for clustering at the herd level. First test and whole-lactation milk and component yields were lowest for SDSG. Within cows that experienced calving difficulty, rates of receiving first service were 13 and 20% less for SDSG and ADSG compared with ADAG. Hazard of leaving the herd by 60 d in milk (DIM) was 34% greater for ADSG than ADAG. Similar effects between SDSG and ADSG but not SDAG indicated that short GL was a greater contributor to poor performance than DPL itself. Overall production was similar between ADAG and SDAG; however, somatic cell linear score at first test was greater for SDAG, and milk yield at first test was lesser for SDAG cows with greater milk at last test before dry-off. Although short DPL might be a successful strategy for some herds or cows, cows with high milk yield at dry-off should not be subjected to a short dry period. Long DPL or GL did not influence early-lactation or whole-lactation milk yield. Cows with a long DPL due to early dry-off (LDAG) likely experienced issues related to excessive lipid mobilization, as milk fat concentration and fat:protein ratio at first test were greater and hazard of leaving the herd was 30 and 24% greater compared with ADAG by 60 and 365 DIM, respectively. We conclude that deviations in DPL length caused by biology (short GL) were associated with greater effects than management causes of short DPL, whereas management reasons for long DPL were associated with more negative outcomes than long GL.

Preweaning cost of bovine respiratory disease (BRD) and cost-benefit of implementation of preventative measures in calves on California dairies: The BRD 10K study.

Bovine respiratory disease (BRD) is a multifactorial disease that is estimated to affect 22% of preweaned dairy calves in the United States and is a leading cause of preweaning mortality in dairy calves. Overall cost of calfhood BRD is reflected in both the immediate cost of treating the disease as well as lifetime decrease in production and increased likelihood of affected cattle leaving the herd before their second calving. The goal of this paper was to develop an estimate of the cost of BRD based on longitudinal treatment data from a study of BRD with a cohort of 11,470 preweaned dairy calves in California. Additionally, a cost-benefit analysis was performed for 2 different preventative measures for BRD, an increase of 0.47 L of milk per day for all calves or vaccination of all dams with a modified live BRD vaccine, using differing assumptions about birth rate and number of calves raised per year. Average short-term cost of BRD per affected calf was $42.15, including the use of anti-inflammatory medications in the treatment protocols across all management conditions. The cost of treating BRD in calves appears to have increased in recent years and is greater than costs presented in previous studies. A cost-benefit analysis examined different herd scenarios for a range of cumulative incidences of BRD from 3 to 25%. Increasing milk fed was financially beneficial in all scenarios above a 3% cumulative incidence of BRD. Use of a modified live vaccine in dams during pregnancy, examining only its value as a form of BRD prevention in the calves raised on the farm, was financially beneficial only if the cumulative incidence of BRD exceeded 10 to 15% depending on the herd size and whether the dairy farm was raising any bull calves. The cost-benefit analysis, under the conditions studied, suggests that producers with high rates of BRD may benefit financially from implementing preventative measures, whereas these preventative measures may not be cost effective to implement on dairy farms with very low cumulative incidences of BRD. The long-term costs of calfhood BRD on lifetime productivity were not factored into these calculations, and the reduction in disease may be associated with additional cost savings and an improvement in calf welfare and herd life.

Use of a stochastic simulation model to estimate the cost per case of digital dermatitis, sole ulcer, and white line disease by parity group and incidence timing.

A farm-level stochastic simulation model was modified to estimate the cost per case of 3 foot disorders (digital dermatitis, sole ulcer, and white line disease) by parity group and incidence timing. Disorder expenditures considered within the model included therapeutics, outside labor, and on-farm labor. Disorder losses considered within the model included discarded milk, reduced milk production, extended days open, an increased risk of culling, an increased risk of death (natural or euthanized), and disease recurrence. All estimates of expenditures and losses were defined using data from previously published research in stochastic distributions. Stochastic simulation was used to account for variation within the farm model; 1,000 iterations were run. Sensitivity of foot disorder costs to selected market prices (milk price, feed price, replacement heifer price, and slaughter price) and herd-specific performance variables (pregnancy rate) were analyzed. Using our model assumptions, the cost per disorder case over all combinations of parity group and incidence timing, regardless of incidence likelihood, was lowest for digital dermatitis ($64 ± 24; mean ± standard deviation), followed by white line disease ($152 ± 26) and sole ulcer ($178 ± 29). Disorder costs were greater in multiparous versus primiparous cows and were always highest at the beginning of lactation. The greatest contributing cost categories were decreased milk production, an increased risk of culling, and disease recurrence. The contribution of cost categories to the total cost of disorder varied by disorder type, parity group, and incidence timing. For all disorders, the cost per case increased as milk price or replacement heifer price increased and decreased as feed price, pregnancy rate, or slaughter price increased. Understanding how foot disorder costs change according to cow-specific conditions (i.e., disorder type, parity group, and days in milk at incidence) and herd-specific conditions (i.e., market prices and performance variables) can help improve on-farm decisions about treatment and prevention of foot disorders.

Estimating the value of infectious or noninfectious foot disorder prevention strategies within dairy farms, as influenced by foot disorder incidence rates and prevention effectiveness.

A farm-level stochastic simulation model was adapted to estimate the value of implementing foot disorder prevention on a dairy farm by calculating the return on investment associated with implementation of foot disorder prevention. Two potential strategies for foot disorder prevention were tested: strategy 1 was prevention focused on reducing infectious foot disorders (i.e., digital dermatitis) in the model, and strategy 2 was prevention focused on reducing noninfectious foot disorders (i.e., sole ulcer and white line disease) in the model. For each strategy, we evaluated the effect of foot disorder incidence on the value of prevention by setting the incidence of foot disorders at 3 levels. For strategy 1, the level of digital dermatitis incidence without prevention in all parities was 20, 40, or 60%, and the incidence level of the noninfectious foot disorders in the model were held constant. For strategy 2, levels of sole ulcer and white line disease incidence without prevention in parity ≥3 cows were 5, 15, or 25%, and the incidence level of the infectious foot disorders included in the model were held constant; the incidence levels of noninfectious foot disorders in younger cows were adjusted to be lower. Overall, 6 scenarios were run, 1 for each prevention strategy × foot disorder incidence rate combination. To evaluate how the effectiveness of each prevention strategy would influence the investment value, the effectiveness of prevention could vary from a prevention risk ratio (RR) of 0.0 (100% reduction in disorder incidence) to 1.0 (0% reduction in disorder incidence). When implementing strategy 1, the return on prevention investment per cow-year (mean ± standard deviation) when prevention effectiveness was low (prevention RR = 0.91 to 1.0) and the digital dermatitis incidence rate was originally 20, 40, or 60% was $0.6 ± 0.4, $1.2 ± 0.9, and $1.8 ± 1.3, respectively. In comparison, the return on prevention investment per cow-year when prevention effectiveness was high (prevention RR = 0.00 to 0.09) and the digital dermatitis incidence rate was originally 20, 40, or 60% was $12.2 ± 3.0, $24.4 ± 6.0, and $36.5 ± 9.0, respectively. When implementing strategy 2, the return on prevention investment per cow-year when prevention effectiveness was low and noninfectious foot disorder incidence rates were originally 5, 15, or 25% in parity ≥3 cows was $0.6 ± 0.4, $1.9 ± 1.1, and $3.2 ± 1.9, respectively. In comparison, the return on prevention investment per cow-year when prevention effectiveness was high and noninfectious foot disorder incidence rates were originally 5, 15, or 25% in parity ≥3 cows was $12.4 ± 1.5, $37.3 ± 4.6, and $62.2 ± 7.6, respectively. The return on investment for foot disorder prevention would depend on the cost of the prevention strategy and the other benefits associated with the selected prevention strategy. This model could be used as a decision support tool to help identify the amount that could be paid to implement a selected prevention strategy.

Effect of health status upon arrival at a single milk-fed veal facility on breakeven purchase price of calves.

Male calves are purchased from the dairy industry in North America to produce red meat. The price paid for male calves varies widely, and it is unclear which variables influence the price paid for each calf. The objective of this study was to assess how the health traits of calves at the time of arrival and demographic variables affect the breakeven purchase price of a male calf entering the veal industry. A financial model was constructed using the prevalence of health abnormalities, weight at arrival, source of the calf, number of days in the barn, base carcass price, days to mortality, feed costs, season at arrival, interest rate, housing location, carcass dressing percentage, and costs associated with housing, labor, utilities, trucking, and health to calculate the breakeven purchase price and an estimate of profit. Sensitivity analysis was conducted using health variables measured at arrival and demographic variables, including season at arrival and housing location, to identify the factors with the largest impact on the predicted average daily gain, early and late mortality risk, breakeven purchase price, and profit. At the baseline inputs, the average calculated profit was -$5.36 per calf and it was most sensitive to the location of housing where calves were fed and the body weight of the arriving calf. The mortality risk in the first 21 d after arrival (early) was calculated to be 2.2%, whereas the risk of mortality after 21 d (late) was 3.7%. The risks of early and late mortality were most sensitive to the level of dehydration measured at arrival and the season at arrival for the purchased calves, respectively. The calculated average daily gain was 1.12 kg/d and it was most sensitive to housing location. The breakeven purchase price was calculated to be $242.49 per calf, which was most sensitive to the housing location where the calves were fed. The results of this analysis demonstrate that veal producers need to consider many variables before purchasing calves. In addition to overall market conditions, veal producers should factor health characteristics and the expected performance of the calves they purchase into what they are willing to pay for them.

Short communication: Model for metritis severity predicts that disease misclassification underestimates projected milk production losses.

The objective of this research was to determine the effect of disease misclassification on the estimated effect of metritis on milk production. Misclassification introduces bias that usually results in an underestimation of the association between exposure (disease) and the outcome of interest (milk production). This distorted measure of association results from the comparison of an affected population (some of which may not truly be affected) to a nonaffected population (which often includes affected subjects that are unidentified). A convenience sample of DairyComp305 (Valley Agricultural Software, Tulare, CA) data representing 1 yr of calvings (n = 3,277) from 1 Midwestern Holstein herd was used. This herd was chosen because of its ongoing efforts to consistently and completely record all clinical diseases, including the incidence of both mild and severe metritis cases. Metritis was defined as the presence of a flaccid uterus containing fetid fluids or a foul watery discharge within 14 d of calving. Cows that appeared clinically normal other than the discharge were considered mild and those with systemic signs of disease were classified as severe. The original data set included metritis recorded as mild, severe, or not recorded (NR), where no metritis was observed, and was considered to contain the metritis true severity (TrS). First, to evaluate the effect of misclassification bias, we retrospectively randomized 45% of mild metritis to be classified as NR to simulate inconsistent disease recording (IR); then, in a separate model, all mild metritis cases were changed to NR to simulate a situation of very poor disease recording (PR), where only the most severe cases are recorded. The TrS, IR, and PR data sets were analyzed separately in JMP (SAS Institute Inc., Cary, NC). An ANOVA was conducted for second test 305-d mature-equivalent milk projection (2nd305ME), and nonsignificant variables were removed, but the variable metritis was forced into all models. Based upon the TrS model, adjusting for effects of lactation group, month of calving, dystocia, twins, retained placenta, early-lactation mastitis, displaced abomasum, and significant interactions, a case of mild metritis was associated with 384 kg less 2nd305ME and a case of severe metritis was associated with 847 kg less 2nd305ME compared with no metritis. For the IR model, a case of mild metritis was associated with 315 kg less 2nd305ME and a case of severe metritis was associated with 758 kg less 2nd305ME compared with no metritis. For the PR model, severe metritis was associated with 680 kg less 2nd305ME compared with NR. The IR and PR models underestimated 2nd305ME loss for severe metritis cases by 89 and 166 kg/cow, and resulted in 180,441 and 330,256 kg of total milk loss unaccounted for at the herd level, respectively, compared with TrS. Overall, misclassification of metritis cases results in greater bias and largely underestimates the true association between metritis and the consequence costs of the disease.

A survey of United States dairy hoof care professionals on costs associated with treatment of foot disorders.

The objective of this study was to collect information regarding hoof care professionals' billing practices and to gather their opinions about foot disorders and the value of their prevention. Responses were gathered from veterinarians (n = 18) and hoof trimmers (n = 116) through both online and paper survey platforms. Because of the limited number of respondents, veterinarian responses were not further analyzed. Of the 6 foot disorders included in the survey, the treatment cost per case was greatest for toe ulcers (mean ± standard deviation; $20.2 ± 8.5), sole ulcers ($19.7 ± 8.6), white line disease ($19.5 ± 8.1), and thin soles ($18.1 ± 8.1), and least for infectious disorders (foot rot and digital dermatitis; $8.0 ± 7.6 and $7.5 ± 9.6, respectively). Of the disorders, digital dermatitis represented most of the foot disorder cases treated by respondents over the past year (43.9 ± 20.4%), whereas toe ulcers and thin soles represented the least (5.3 ± 4.1 and 5.3 ± 5.7%, respectively). Respondents that served mostly large herds (>500 lactating cows) reported a lower prevalence of digital dermatitis (31.6 ± 4.2 vs. 44.4 ± 3.4 and 46.7 ± 3.2% in small and medium herds, respectively) and a higher prevalence of sole ulcers (23.1 ± 3.0 vs. 13.4 ± 2.4 and 13.3 ± 2.3% in small and medium herds, respectively). Region of the United States (Northeast, Midwest, or other) also influenced foot disorder prevalence; respondents from the Northeast reported more sole ulcers than respondents from other regions (22.1 ± 2.3 vs. 12.4 ± 3.3%). When respondents were asked which disorder was associated with the greatest total cost per case to the producer (treatment and labor costs plus the reduction in milk yield, reduced reproductive performance, and so on), hoof trimmers ranked digital dermatitis as having the greatest total cost per case and thin soles as having the least total cost per case. Finally, respondents indicated that the most important benefits of reducing foot disorders were enhanced animal welfare and increased milk production, whereas the least important benefit was reduced veterinary and hoof trimmer fees. Results from this survey can be used to improve the accuracy of foot disorder cost estimates and contribute to better decision-making regarding both foot disorder treatment and prevention.

Effect of health status evaluated at arrival on growth in milk-fed veal calves: A prospective single cohort study.

The objective of this prospective single cohort study was to determine the effect of health status at arrival on growth in milk-fed veal calves. Upon arrival at the veal facility, calves were evaluated using a standardized health scoring system and weighed, and the supplier of the calf was recorded. The calves were followed until slaughter, when the hot carcass weight (HCW) was reported. To calculate average daily gain (ADG), the HCW was transformed into an estimated live weight, weight at arrival was subtracted, and this value was divided by the number of days on feed. A mixed linear regression model was created to evaluate the association of health status on arrival with the ADG throughout the production period. A total of 4,825 calves were evaluated at arrival; however, due to inconsistent HCW data from one slaughter plant, and 357 calves dying during the production period, 2,283 calves were used for analysis. In the final model, 7 variables were significantly associated with ADG. Housing location within the farm, method of calf procurement (drover or auction-derived calves versus direct delivery from local farms) and having a higher body weight at arrival were associated with a higher ADG. The season of arrival (summer or fall compared with winter) and being dehydrated at arrival were associated with a lower ADG. Days on feed was also significant in the multivariable model and had a quadratic relationship with ADG. The associations identified suggest that there may be value in scoring dehydration and body weight at arrival to a veal facility.

Short communication: Effect of cross ventilation with or without evaporative pads on core body temperature and resting time of lactating cows.

A trial was performed to assess the effect of evaporative pads on core body temperature (CBT) and lying behavior of lactating Holstein cows housed in cross-ventilated freestall facilities in a humid environment. This trial was undertaken in 2 barns equipped with (EP) or without (NP) evaporative pads. Each facility had 4 pens, 1 baffle/pen, and a nominal width of 122 m. Stocking density was higher (123.4 vs. 113.1%) and freestalls were slightly shorter (2.3 vs. 2.4 m) and narrower (1.16 vs. 1.21 m) in EP compared with NP barns. In each pen, lying behavior of 20 cows was monitored using electronic data loggers that recorded at 1-min intervals. A subset (n=14) of these cows within each pen were also fitted with temperature loggers attached to blank controlled intravaginal drug release devices to determine CBT every 5 min. Ambient conditions were collected every 15 min. Individual cow lying duration and lying bouts were assessed for each cow, as well as time spent standing and CBT within the following categories: CBT <38.6°C, and CBT >38.6, >38.9, >39.2, >39.4, and >39.7°C. These variables were analyzed using pen as the experimental unit, with cow and day as additional random effects. The average maximum ambient conditions over the 9 d were 25°C and 78.74% relative humidity. No differences were observed in lying duration and number of lying bouts over the 9-d period, with overall means of 696±31 min/d and 12.6±0.5 bouts/d. The EP cows spent 170 min/d longer with a CBT <38.6°C and 107 min/d less with CBT >39.2°C than did NP cows. Cooling with evaporative pads tended to increase time spent lying with a CBT >8.6°C and lying bouts/d for EP cows versus NP cows. Results from this trial show that even under mild heat stress, evaporative cooling in cross-ventilated facilities can decrease CBT and tended to increase lying time.

Hyperketonemia in early lactation dairy cattle: a deterministic estimate of component and total cost per case.

The purpose of this study was to develop a deterministic economic model to estimate the costs associated with (1) the component cost per case of hyperketonemia (HYK) and (2) the total cost per case of HYK when accounting for costs related to HYK-attributed diseases. Data from current literature was used to model the incidence and risks of HYK (defined as a blood ß-hydroxybutyrate concentration≥1.2 mmol/L), displaced abomasa (DA), metritis, disease associations, milk production, culling, and reproductive outcomes. The component cost of HYK was estimated based on 1,000 calvings per year; the incidence of HYK in primiparous and multiparous animals; the percent of animals receiving clinical treatment; the direct costs of diagnostics, therapeutics, labor, and death loss; and the indirect costs of future milk production losses, future culling losses, and reproduction losses. Costs attributable to DA and metritis were estimated based on the incidence of each disease in the first 30 DIM; the number of cases of each disease attributable to HYK; the direct costs of diagnostics, therapeutics, discarded milk during treatment and the withdrawal period, veterinary service (DA only), and death loss; and the indirect costs of future milk production losses, future culling losses, and reproduction losses. The component cost per case of HYK was estimated at $134 and $111 for primiparous and multiparous animals, respectively; the average component cost per case of HYK was estimated to be $117. Thirty-four percent of the component cost of HYK was due to future reproductive losses, 26% to death loss, 26% to future milk production losses, 8% to future culling losses, 3% to therapeutics, 2% to labor, and 1% to diagnostics. The total cost per case of HYK was estimated at $375 and $256 for primiparous and multiparous animals, respectively; the average total cost per case of HYK was $289. Forty-one percent of the total cost of HYK was due to the component cost of HYK, 33% to costs attributable to metritis, and 26% to costs attributable to DA. The high total cost of HYK at reported incidences of 40 to 60% highlights the importance of appropriate transition cow nutrition and management to decrease the effect of HYK.

Comparative efficacy of enrofloxacin and tulathromycin for treatment of preweaning respiratory disease in dairy heifers.

Preweaning respiratory disease continues to have a substantial effect on the current and future productivity of dairy replacement animals. Establishing an effective treatment plan for the preweaned calf may have a significant effect on well-being and lifetime productivity by limiting any early development of chronic disease. The primary objective of this study was to examine the efficacy of treatment with tulathromycin (TUL) or enrofloxacin (ENR) on the risk of re-treatment, with a secondary objective of investigating the effect of disease and subsequent treatment choice on average daily gain (ADG). A total of 1,141 Holstein heifers from 4 farms were observed and systematically scored for evidence of respiratory disease from birth through weaning or the time of death. At the time of diagnosis, calves were randomly and blindly allocated into 2 treatment groups. The overall incidence of respiratory disease was 60.9%. In the univariable analysis, the incidence of re-treatment between 7 and 10d of initial therapy for calves treated with ENR was greater than that in calves treated with TUL (27.6 vs. 21.2%). After adjusting for farm ID, clinical score at first treatment, and weight at first treatment, the odds of re-treatment were 1.5 times higher for calves treated with ENR than with TUL. The percentage of calves that required more than one re-treatment was higher for calves that received ENR compared with those that received TUL (9.3 vs. 4.1%). We observed no difference in ADG between calves treated with ENR or TUL, and no difference in ADG between calves that were treated for respiratory disease and those that were not treated for respiratory disease. Appropriate drug therapy for preweaning respiratory disease may have an important role in reducing the odds of re-treatment during the preweaning period.

Effect of prepartum administration of recombinant bovine somatotropin on health and performance of lactating dairy cows.

A double-blind, randomized clinical trial was conducted in 5 commercial dairy herds in southern Ontario with 1,362 cows enrolled to evaluate the effect of prepartum administration of recombinant bovine somatotropin (rbST) on health and performance. Cows were randomly assigned to receive either 325 mg of sometribove zinc suspension (n=680) or a placebo injection (n=682; control) subcutaneously every 14 d until calving. Treatments started 28 to 22 d before expected calving, with a maximum of 3 treatments per cow. Serum samples taken at the time of enrollment, 1 wk before calving, and weekly for 3 wk after calving were analyzed for nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), glucose, aspartate aminotransferase, calcium, and haptoglobin. Diseases were recorded by farm staff. Incidences of clinical ketosis, clinical mastitis, displaced abomasum, metritis, retained placenta, milk fever, and lameness were similar between groups. Body condition score was lower for treated than for control cows at 3 wk after calving (3.13 and 3.17, respectively). Serum NEFA tended to be higher for treated than for control cows by 0.01 mmol/L. Overall BHBA was not different between groups, but BHBA for treated cows was higher in wk 1 after calving (750 and 698 µmol/L, respectively) and tended to be higher in wk 2 after calving (779 and 735 µmol/L, respectively). Incidence of hyperketonemia was similar between groups. Treated cows had higher serum glucose compared with control cows (2.8 and 2.7 mmol/L, respectively). We detected no differences in serum aspartate aminotransferase, calcium, or haptoglobin between groups. Milk yield was recorded daily for each cow for 63 d, and did not differ between groups (37.1 ± 0.5 kg and 36.7 ± 0.5 kg, respectively) but we detected a tendency for treated cows to produce 0.8 kg/d more milk than control cows in wk 1 after calving. We observed no difference between groups in the time from calving to first insemination or the probability of pregnancy at the first insemination. Groups did not differ in the proportion of anovular cows at 53 ± 3 d in milk based on serum progesterone measured from a subset of cows (38.0 and 34.3%, respectively, for treated and control groups). We found no difference between groups in dry matter intake from 21 d before calving to 63 d after calving in a subset of cows (17.4 ± 0.4 and 17.5 ± 0.4 kg/d, respectively). Based on results of the current study, biweekly (every 14 d) administration of rbST before calving to prevent disease and enhance performance is not recommended.

The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance.

The objective was to examine the associations of peripartum concentrations of nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), and calcium with milk production in early lactation and pregnancy at the first artificial insemination (AI) across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were visited weekly for blood sample collection from 2,365 cows. For each week of sampling (from wk -1 through wk 3 relative to calving) and for each metabolite, serum concentrations were dichotomized at various thresholds to identify the thresholds with the best negative associations with milk production and pregnancy at first AI. These thresholds were used to categorize the serum concentrations into higher and lower risk categories. Repeated-measures ANOVA and multivariable logistic regression were conducted for milk production and pregnancy at the first AI data, respectively, considering cow as the experimental unit and herd as a random effect. In the week before calving, serum NEFA ≥ 0.5 mEq/L, BHBA ≥ 600 µmol/L, and calcium ≤ 2.1 mmol/L were associated with 1.6 to 3.2 kg/d milk loss across the first 4 Dairy Herd Improvement Association (DHIA) milk tests. High levels of NEFA and BHBA in wk 1 and 2 after calving (≥ 0.7 and ≥ 1.0 mEq/L for NEFA, and ≥ 1,400 and ≥ 1,200 µmol/L for BHBA), and low levels of calcium (≤ 2.1 mmol/L) in wk 1, 2 and 3 after calving were associated with milk loss at the first DHIA milk test. Serum concentrations of NEFA and BHBA were not associated with pregnancy at first AI in any sampling week, whereas calcium <2.2 to 2.4 mmol/L from wk 1 through wk 3 postpartum were associated with reduced pregnancy at first AI. In conclusion, high serum concentrations of NEFA, BHBA, and low concentrations of calcium around parturition were associated with early lactation milk loss, and low calcium concentration around parturition was associated with impaired early lactation reproduction.

Herd-level association of serum metabolites in the transition period with disease, milk production, and early lactation reproductive performance.

The objective was to identify herd-level indicators expressed as a proportion of sampled animals with increased nonesterified fatty acids (NEFA) or ß-hydroxybutyric acid (BHBA), or decreased calcium in wk -1 and wk +1 relative to calving that were associated with herd-level incidence of retained placenta, metritis and displaced abomasum, milk production, and probability of pregnancy at the first artificial insemination (AI). Fifty-five Holstein freestall dairy herds in the United States and Canada were visited weekly. Blood was collected from 2,365 cows around parturition, and serum concentrations of NEFA, BHBA, and calcium were determined. Different cow-level metabolite thresholds associated with detrimental health or productivity in previous studies were used to classify animals into high- and low-risk metabolite concentration groups. For wk -1 and wk +1 relative to calving, a herd-level threshold was determined as the proportion of sampled animals in the high-risk metabolite concentration groups with the strongest association with increased incidence of disease, milk loss, or decreased pregnancy at the first AI. The odds of displaced abomasum after calving were higher in herds that had ≥ 25% of the animals with BHBA ≥ 1,400 µmol/L in wk +1 [odds ratio (OR)=2.1; 95% confidence interval (CI)=1.0-4.2)] or ≥ 35% of the animals with calcium ≤ 2.1 mmol/L in wk +1 (OR=2.4; CI=1.3-4.3). Herd-level thresholds of ≥15% of the cows with BHBA ≥ 800 µmol/L in wk -1 and ≥ 15% of the cows with calcium ≤2.1mmol/L in wk +1 were associated with milk loss (±SE) of 4.4±1.7 and 3.8 ± 1.4 kg/d per cow, respectively. When only multiparous cows were considered, herds with ≥30% of the multiparous cows with NEFA ≥0.5 mEq/L in wk -1 were associated with a 3.0 ± 1.5 kg/d per cow milk loss. The odds of pregnancy at first AI were lower in herds that had ≥ 5% of the cows with calcium ≤ 2.1 mmol/L in wk -1 (OR=0.7; CI=0.5-1.0), or ≥ 30% of the cows with NEFA ≥ 1.0 mEq/L (OR=0.6; CI=0.4-0.9) or ≥ 25% of the cows with calcium ≤2.1 mmol/L in wk +1 (OR=0.7; CI=0.5-0.9). When only multiparous cows were considered, the odds of pregnancy at first AI were lower in herds that had ≥50% of multiparous cows with NEFA ≥0.5 mEq/L in wk -1 (OR=0.5; CI=0.2-0.9). In conclusion, several herd-level thresholds for the proportion of cows with increased NEFA or BHBA, or decreased calcium in the week before and after calving were associated with higher risk of displaced abomasum, milk loss at the first Dairy Herd Improvement Association test, and decreased pregnancy at first AI. The association found between precalving BHBA and milk production is promising due to the availability of several cow-side tests for measuring BHBA. Some of the herd-level associations differed from the previously described cow-level associations, suggesting the potential of interpreting periparturient metabolic challenges at the herd level, where changes in diet and management are generally implemented.

The association of serum metabolites with clinical disease during the transition period.

The objective of this observational field study was to validate the relationship of serum concentrations of nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), and calcium with disease in early lactation across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were selected and visited weekly for blood sample collection from 2,365 cows. Only diseases that were consistently recorded across herds and blood samples collected before the disease occurred were considered. Metabolite concentrations in serum in wk -1 relative to calving were considered as predictors of retained placenta (RP) and metritis, and metabolite concentrations in serum in wk -1 and wk +1 relative to calving were considered as predictors of displaced abomasum (DA). For each disease, each metabolite, and week of sampling in the case of DA, a critical threshold was calculated based on the highest combined sensitivity and specificity and used to categorize the serum concentrations into high and low risk categories. Multivariable logistic regression models were built for each disease of interest and week of sampling, considering cow as the experimental unit and herd as a random effect. Cows with precalving serum NEFA concentrations ≥ 0.3 mEq/L were more likely to develop RP [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.3 to 2.6] and metritis (OR = 1.8; 95% CI = 1.5 to 2.9) after calving than cows with lower NEFA concentrations. Precalving NEFA ≥ 0.5 mEq/L (OR = 2.4; 95% CI = 1.5 to 3.7), postcalving NEFA ≥ 1.0 mEq/L (OR = 2.7; 95% CI = 1.7 to 4.4), and postcalving calcium ≤ 2.2 mmol/L (OR = 3.1; 95% CI = 1.9 to 5.0) were associated with subsequent risk of DA. In conclusion, elevated serum NEFA concentrations within 1 wk before calving were associated with increased risk of RP, metritis, and DA after calving. Serum NEFA and calcium concentrations in the 2 wk around calving in combination were associated with the risk of DA.

The effect of injectable butaphosphan and cyanocobalamin on postpartum serum beta-hydroxybutyrate, calcium, and phosphorus concentrations in dairy cattle.

The objective of this study was to determine the effect of an injection of 10% butaphosphan and cyanocobalamin (Catosal, Bayer, Shawnee Mission, KS) on the day of calving and 1 d later on the prevalence of subclinical ketosis in dairy cattle in the early postpartum period. Cows from 4 herds (n=1,122) were randomized to receive either 25mL of 10% butaphosphan and cyanocobalamin or 25mL of sterile water subcutaneously on both days. Each milliliter of Catosal contained 0.05mg of cyanocobalamin and 100mg of butaphosphan, which provided 17.3mg of P in the form of [1-(butylamino)-1-methylethyl]-phosphonic acid. Serum was sampled for beta-hydroxybutyrate (BHBA) concentration at calving (pretreatment) and again between 3 and 10 d in milk. A subset of samples from mature cows was also evaluated for serum Ca and P concentrations. When cows from all age groups were included in the analysis, there was no difference between the median serum BHBA concentrations of cows in the 2 treatment groups, and no difference in the proportion of hyperketonemic cows (serum BHBA >or=1,200micromol/L) during the first week postpartum. When the analysis was restricted to mature cows (lactation >or=3), both the median BHBA concentration and the proportion of hyperketonemic cows were significantly lower in the treatment group than in the placebo group. Serum Ca and P concentrations did not differ between treatment groups. Our results suggest that injection of butaphosphan and cyanocobalamin on the day of calving and 1 d later may decrease the prevalence of subclinical ketosis during the week after calving in mature dairy cows, but not in first- and second-lactation animals.

Exploring the impact of sexed semen on the structure of the dairy industry.

Widespread commercial application of sexed semen is expected within the next decade because of continued improvements in fertility of sexed semen and sorting capacity. The objective of this study was to explore the potential impact of widespread application of sexed semen on the structure of the dairy industry in the United States. Historically, female offspring from all heifers and cows were needed to produce enough dairy replacement heifers to replace culled cows. The use of sexed semen allows for a decoupling of breeding decisions necessary to obtain an adequate supply of dairy replacement heifers from those needed to achieve pregnancies needed to start new lactations. Application of sexed semen allows dairy producers to select among their herds' potential dams and produce dairy replacement heifers from only the genetically superior animals. The rate of genetic progress is expected to increase, but not more than 15% of the rate of gain accomplished through sire selection achieved through conventional (nonsexed) artificial insemination breeding. The supply of dairy replacement heifers is expected to grow to meet and temporarily exceed current demand, resulting in reduced prices for dairy replacement heifers. Consequently, herd turnover rates are expected to increase slightly, and herd expansions may accelerate. The rate of consolidation of dairy farms is expected to increase. Widespread application of sexed semen may temporarily increase the supply of milk, which would result in lower milk prices. The cost of milk production will be reduced as well. Many breeding options exist for the genetically poorer cows in the herd. The optimal breeding mix depends on the value of the various kinds of calves that could be produced. More crossbred calves for beef production may be produced; however, a market for these crossbred calves is not well established. Increased specialization is expected with more dairy producers deciding not to raise their own heifers but to purchase replacements. Other dairy farms might specialize in producing genetically superior dairy replacement heifers for sale. Depending on the value of calves not raised for replacements, artificial insemination organizations might market beef conventional semen or beef male sexed semen to dairy farms. The use of sexed semen should lower the cost of progeny-testing programs and embryo transfer and enhance the value of genetic markers. Eventually, the economic benefits from the use of sexed semen will be passed on to consumers.

G-protein-coupled receptors function as oligomers in vivo.

Hormones, sensory stimuli, neurotransmitters and chemokines signal by activating G-protein-coupled receptors (GPCRs) [1]. Although GPCRs are thought to function as monomers, they can form SDS-resistant dimers, and coexpression of two non-functional or related GPCRs can result in rescue of activity or modification of function [2-10]. Furthermore, dimerization of peptides corresponding to the third cytoplasmic loops of GPCRs increases their potency as activators of G proteins in vitro [11], and peptide inhibitors of dimerization diminish beta(2)-adrenergic receptor signaling [3]. Nevertheless, it is not known whether GPCRs exist as monomers or oligomers in intact cells and membranes, whether agonist binding regulates monomer-oligomer equilibrium, or whether oligomerization governs GPCR function. Here, we report that the alpha-factor receptor, a GPCR that is the product of the STE2 gene in the yeast Saccharomyces cerevisiae, is oligomeric in intact cells and membranes. Coexpression of receptors tagged with the cyan or yellow fluorescent proteins (CFP or YFP) resulted in efficient fluorescence resonance energy transfer (FRET) due to stable association rather than collisional interaction. Monomer-oligomer equilibrium was unaffected by binding of agonist, antagonist, or G protein heterotrimers. Oligomerization was further demonstrated by rescuing endocytosis-defective receptors with coexpressed wild-type receptors. Dominant-interfering receptor mutants inhibited signaling by interacting with wild-type receptors rather than by sequestering G protein heterotrimers. We suggest that oligomerization is likely to govern GPCR signaling and regulation.

Mechanisms governing the activation and trafficking of yeast G protein-coupled receptors.

We have addressed the mechanisms governing the activation and trafficking of G protein-coupled receptors (GPCRs) by analyzing constitutively active mating pheromone receptors (Ste2p and Ste3p) of the yeast Saccharomyces cerevisiae. Substitution of the highly conserved proline residue in transmembrane segment VI of these receptors causes constitutive signaling. This proline residue may facilitate folding of GPCRs into native, inactive conformations, and/or mediate agonist-induced structural changes leading to G protein activation. Constitutive signaling by mutant receptors is suppressed upon coexpression with wild-type, but not G protein coupling-defective, receptors. Wild-type receptors may therefore sequester a limiting pool of G proteins; this apparent "precoupling" of receptors and G proteins could facilitate signal production at sites where cell surface projections form during mating partner discrimination. Finally, rather than being expressed mainly at the cell surface, constitutively active pheromone receptors accumulate in post-endoplasmic reticulum compartments. This is in contrast to other defective membrane proteins, which apparently are targeted by default to the vacuole. We suggest that the quality-control mechanism that retains receptors in post-endoplasmic reticulum compartments may normally allow wild-type receptors to fold into their native, fully inactive conformations before reaching the cell surface. This may ensure that receptors do not trigger a response in the absence of agonist.