m self-reported performance levels. Rearing practices found to be associated with higher farm performance could be targeted by advisory services to help improve management practices on Canadian dairy goat farms.The objective of this randomized, double-blind, controlled trial was to evaluate the effect of pegbovigrastim (pegylated recombinant bovine granulocyte colony-stimulating factor) on early-lactation disease, milk yield, and reproduction on commercial dairy farms. A total of 1,607 Holstein cows from 6 farms in Ontario and Québec, Canada, were randomly assigned to receive two 2.7-mL subcutaneous injections of either 15 mg of pegbovigrastim (n = 798; Imrestor, Elanco) or sterile physiological saline (placebo; n = 809). The first injection was administered by investigators 1 wk before expected calving, and the second by farm personnel within 24 h after calving, according to the product label. Producers inspected cows daily and using standardized disease definitions, recorded cases of retained placenta, metritis, displaced abomasum, and clinical mastitis until 63 d in milk. Progesterone concentration was measured in serum at wk 3, 5, 7, and 9 postpartum. Cows were examined for purulent vaginal discharge using the Me, slightly reduced the concentration of albumin, and slightly increased concentrations of β-hydroxybutyrate and nonesterified fatty acids, with no effect on the other markers. There were no differences between treatments in culling risk, time to first insemination, pregnancy at first insemination, or time to pregnancy. Milk yield over the first 3 test days of lactation was 1.0 kg per day lower in the pegbovigrastim group, although a mechanism for that effect could not be explained through analysis of our data.Suppression of appetite, or hypophagia, is among the most recognizable effects of disease in livestock, with the potential to impair growth, reproduction, and lactation. The continued evolution of the field of immunology has led to a greater understanding of the immune and endocrine signaling networks underlying this conserved response to disease. Inflammatory mediators, especially including the cytokines tumor necrosis factor-α and interleukin-1β, are likely pivotal to disease-induced hypophagia, based on findings in both rodents and cattle. However, the specific mechanisms linking a cytokine surge to decreased feeding behavior are more difficult to pin down and likely include direct effects on appetite centers in the brain, alteration of gastric motility, and modulation of other endocrine factors that influence appetite and satiety. These insights into the mechanisms for disease-induced hypophagia have great relevance for management of neonatal calves, mature cows transitioning to lactation, and cows experiencing mastitis; however, it is not necessarily the case that increasing feed intake by any means possible will improve health outcomes for diseased cattle. We explore conflicting effects of hypophagia on immune responses, which may be impaired by the lack of specific substrates, versus apparent benefits for controlling the growth of some pathogens. Anti-inflammatory strategies have shown promise for promoting recovery of feed intake following some conditions but not others. Finally, we explore the potential for early disease detection through automated monitoring of feeding behavior and consider which strategies may be implemented to respond to early hypophagia.The objective of this experiment was to determine the effect of increasing digestible His (dHis) levels with a rumen-protected (RP) His product on milk production, milk composition, and plasma AA concentrations in lactating dairy cows fed a metabolizable protein (MP)-deficient diet, according to the National Research Council dairy model from 2001. The companion paper presents results on the effect of increasing dHis dose with a MP-adequate basal diet. Twenty Holstein cows, of which 8 were rumen-cannulated, were used in a replicated 4 × 4 Latin square design experiment with four 28-d periods. Treatments were a control diet supplying 1.8% dHis of MP or 37 g/d (dHis1.8) and the control diet supplemented RP-His to provide 2.2, 2.6, or 3.0%, dHis of MP, or 53, 63, and 74 g/d (dHis2.2, dHis2.6, and dHis3.0, respectively). Histidine dose did not affect dry matter intake, but milk yield increased quadratically and energy-corrected milk yield increased linearly with increasing dHis dose. Histidine dose had a quadratic effect on milk fat concentration but did not affect milk fat yield. Lactose concentration decreased linearly, whereas lactose yield increased linearly with increasing dHis dose. There was a tendency for a linear increase in milk true protein concentration, and milk true protein yield increased linearly with dHis dose. Further, plasma His concentration increased linearly with increasing dHis dose and calculated apparent efficiency of His utilization decreased quadratically with increasing dHis supply. Histidine had minor or no effects on rumen fermentation. In the conditions of this experiment, RP-His supplementation of an MP-deficient corn silage-based diet increased milk yield linearly up to a dHis supply of 63 g/d (or 2.6% dHis of MP) and increased feed efficiency, energy-corrected milk yield and milk true protein yield linearly up to a dHis supply of 74 g/d (or 3.0% dHis of MP) in lactating dairy cows.The growing amount of genomic information in dairy cattle has increased computational and modeling challenges in the single-step evaluations. The computational challenges are due to the dense inverses of genomic (G) and pedigree (A22) relationship matrices of genotyped animals in the single-step mixed model equations. buy Eribulin An equivalent mixed model equation is given by single-step genomic BLUP that are based on the T matrix (ssGTBLUP), where these inverses are avoided by expressing G-1 through a product of 2 rectangular matrices, and (A22)-1 through sparse matrix blocks of the inverse of full relationship matrix A-1. A proper way to account genetic groups through unknown parent groups (UPG) after the Quaas-Pollak transformation (QP) is one key factor in a single-step model. When the UPG effects are incompletely accounted, the iterative solving method may have convergence problems. In this study, we investigated computational and predictive performance of ssGTBLUP with residual polygenic (RPG) effect and UPG. The QP transformation used A-1 and, in the complete form, T and (A22)-1 matrices as well.