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Context: In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).Objective: To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.Design, Setting, and Participants: Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).Intervention: Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.Main Outcome Measures: Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.Results: At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.Conclusions: The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is a common lung disease of premature infants. Hyperoxia exposure and microbial dysbiosis are contributors to BPD development. However, the mechanisms linking pulmonary microbial dysbiosis to worsening lung injury are unknown. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates oxidative stress responses and modulates hyperoxia-induced lung injury. We hypothesized that airway dysbiosis would attenuate Nrf2-dependent antioxidant function, resulting in a more severe phenotype of BPD. Here, we show that preterm infants with a Gammaproteobacteria-predominant dysbiosis have increased endotoxin in tracheal aspirates, and mice monocolonized with the representative Gammaproteobacteria Escherichia coli show increased tissue damage compared with germ-free (GF) control mice. Furthermore, we show Nrf2-deficient mice have worse lung structure and function after exposure to hyperoxia when the airway microbiome is augmented with E. coli . To confirm the disease-initiating potential of airway dysbiosis, we developed a novel humanized mouse model by colonizing GF mice with tracheal aspirates from human infants with or without severe BPD, producing gnotobiotic mice with BPD-associated and non-BPD-associated lung microbiomes. After hyperoxia exposure, BPD-associated mice demonstrated a more severe BPD phenotype and increased expression of Nrf2 -regulated genes, compared with GF and non-BPD-associated mice. Furthermore, augmenting Nrf2 -mediated antioxidant activity by supporting colonization with Lactobacillus species improved dysbiotic-augmented lung injury. Our results demonstrate that a lack of protective pulmonary microbiome signature attenuates an Nrf2 -mediated antioxidant response, which is augmented by a respiratory probiotic blend. We anticipate antioxidant pathways will be major targets of future microbiome-based therapeutics for respiratory disease.

Objectives: Our objective with this quality improvement initiative was to reduce rates of severe intracranial hemorrhage (ICH) or death in the first week after birth among extremely preterm infants., Methods: The quality improvement initiative was conducted from April 2014 to September 2020 at the University of Alabama at Birmingham's NICU. All actively treated inborn extremely preterm infants without congenital anomalies from 22 + 0/7 to 27 + 6/7 weeks' gestation with a birth weight ≥400 g were included. The primary outcome was severe ICH or death in the first 7 days after birth. Balancing measures included rates of acute kidney injury and spontaneous intestinal perforation. Outcome and process measure data were analyzed by using p-charts., Results: We studied 820 infants with a mean gestational age of 25 + 3/7 weeks and median birth weight of 744 g. The rate of severe ICH or death in the first week after birth decreased from the baseline rate of 27.4% to 15.0%. The rate of severe ICH decreased from a baseline rate of 16.4% to 10.0%. Special cause variation in the rate of severe ICH or death in the first week after birth was observed corresponding with improvement in carbon dioxide and pH targeting, compliance with delayed cord clamping, and expanded use of indomethacin prophylaxis., Conclusions: Implementation of a bundle of evidence-based potentially better practices by using specific electronic order sets was associated with a lower rate of severe ICH or death in the first week among extremely preterm infants., Competing Interests: FINANCIAL DISCLOSURE: Golden Week Program is trademarked with the US Patent and Trademark Office (serial number 87856747). The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Axial spondyloarthritis (axSpA) has strong connections with intestinal inflammation as occurs in Crohn's disease (CD). However, the immunologic mechanisms that distinguish axSpA, CD, and those with features of both diseases (CD-axSpA) are unknown. This study aimed to address this question by initial unbiased single cell RNA-sequencing (scRNAseq) on a pilot cohort followed by validating findings using flow cytometry and ELISA in a larger cohort., Methods: Two individuals each with CD, axSpA, CD-axSpA, and healthy controls (HC) were recruited for a pilot discovery scRNAseq cohort, and the validation cohort consisted of 18 axSpA, 24 CD, 13 CD-axSpA, and 17 HC that was evaluated by flow cytometry on PBMCs and ELISAs for plasma cytokines., Results: Uniquely, PBMCs from subjects with CD-axSpA demonstrated a significant increase in granzyme B+ T cells of both CD4+ and CD8+ lineages by both scRNAseq and flow cytometry. T cell maturation was also greater in those with CD-axSpA, particularly the CD4+ granzyme B+ population. Pathway analysis suggested increased interferon response genes in all immune cell populations within CD-axSpA. Although IFN-γ was elevated in the plasma of a subset of subjects with CD-axSpA, IL-6 was also significantly elevated., Conclusions: Our findings support the presence of a chronic interferonopathy in subjects with CD-axSpA characterized by interferon signaling by pathway analysis and an expansion of mature, cytotoxic T cells. These data indicate fundamental immunological differences between CD-axSpA and both of the putative "parent" conditions, suggesting that it is a distinct disease with unique natural history and treatment needs.

Intestinal microbial dysbiosis, intestinal inflammation, and Th17 immunity are all linked to the pathophysiology of spondyloarthritis (SpA); however, the mechanisms linking them remain unknown. One potential hypothesis suggests that the dysbiotic gut microbiome as a whole produces metabolites that influence human immune cells. To identify potential disease-relevant, microbiome-produced metabolites, we performed metabolomics screening and shotgun metagenomics on paired colon biopsies and fecal samples, respectively, from subjects with axial SpA (axSpA, N=21), Crohn's disease (CD, N=27), and Crohn's-axSpA overlap (CD-axSpA, N=12), as well as controls (HC, N=24). Using LC-MS based metabolomics of 4 non-inflamed pinch biopsies of the distal colon from subjects, we identified significant alterations in tryptophan pathway metabolites, including an expansion of indole-3-acetate (IAA) in axSpA and CD-axSpA compared to HC and CD and indole-3-acetaldehyde (I3Ald) in axSpA and CD-axSpA but not CD compared to HC, suggesting possible specificity to the development of axSpA. We then performed shotgun metagenomics of fecal samples to characterize gut microbial dysbiosis across these disease states. In spite of no significant differences in alpha-diversity among the 4 groups, our results confirmed differences in gene abundances of numerous enzymes involved in tryptophan metabolism. Specifically, gene abundance of indolepyruvate decarboxylase, which generates IAA and I3Ald, was significantly elevated in individuals with axSpA while gene abundances in HC demonstrated a propensity towards tryptophan synthesis. Such genetic changes were not observed in CD, again suggesting disease specificity for axSpA. Given the emerging role of tryptophan and its metabolites in immune function, altogether these data indicate that tryptophan metabolism into I3Ald and then IAA is one mechanism by which the gut microbiome potentially influences the development of axSpA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Berlinberg, Regner, Stahly, Brar, Reisz, Gerich, Fennimore, Scott, Freeman and Kuhn.)

Airway microbial dysbiosis is associated with subsequent bronchopulmonary dysplasia (BPD) development in very preterm infants. However, the relationship of airway microbiome in normal pulmonary development has not been defined. To better understand the role of the airway microbiome, we compared normal and abnormal alveolar and pulmonary vascular development in mice with or without a microbiome. We hypothesized that the lungs of germ-free (GF) mice would have an exaggerated phenotypic response to hyperoxia compared with non-germ-free (NGF) mice. With the use of a novel gnotobiotic hyperoxia chamber, GF and NGF mice were exposed to either normoxia or hyperoxia. Alveolar morphometry, pulmonary mechanics, echocardiograms, inflammatory markers, and measures of pulmonary hypertension were studied. GF and NGF mice in normoxia showed no difference, whereas GF mice in hyperoxia showed protected lung structure and mechanics and decreased markers of inflammation compared with NGF mice. We speculate that an increase in abundance of pathogenic bacteria in NGF mice may play a role in BPD pathogenesis by regulating the proinflammatory signaling and neutrophilic inflammation in lungs. Manipulation of the airway microbiome may be a potential therapeutic intervention in BPD and other lung diseases.

A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery. One of the proposed functions associated with restoration of colonization resistance against C. difficile has been recovery of bile acid metabolism. In this study, we aimed to assess recovery of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial community structure in six patients with recurrent CDI following treatment with FMT over time. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Sustained increases in the levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and variable recovery over time was observed in the secondary bile acids deoxycholate and lithocholate. To correlate these changes with specific microbial taxa at an individual level, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Metabolites that increased following FMT were associated with bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

HIV testing is the gateway into both prevention and treatment services. It is important to understand how men who have sex with men (MSM) perceive HIV self-tests. We conducted focus groups and individual interviews to collect feedback on two HIV self-tests, and on a dried blood spot (DBS) specimen collection kit. Perceptions and attitudes around HIV self-testing (HIVST), and willingness to distribute HIV self-tests to others were assessed. MSM reported HIVST to be complementary to facility-based testing, and liked this approach because it offers privacy and convenience, does not require counseling, and could lead to linkage to care. However, they also had concerns around the accuracy of HIV self-tests, their cost, and receiving a positive test result without immediate access to follow-up services. Despite these issues, they perceived HIVST as a positive addition to their HIV prevention toolbox.

Diverse human tumors obtained directly from surgery or biopsy can grow at high frequency in 3-dimensional Gelfoam ® histoculture for long periods of time and still maintain many of their in vivo properties. The in vivo properties maintained in vitro include 3-dimensional growth; maintenance of tissue organization and structure, such as changes associated with oncogenic transformation; retention of differentiated function; tumorigenicity; and growth of multiple types of cells from a single tumor.

Peer-driven HIV prevention strategies can be effective in identifying high-risk persons with undiagnosed infections. Besides individual self-testing, other potential uses of rapid home HIV test kits include distributing them, and testing with others within one's social or sexual networks. We sought to identify factors associated with the willingness to engage in these alternative activities among men who have sex with men (MSM) in the United States. From May to October 2014, we surveyed 828 HIV-negative or unknown status MSM about multiple aspects of rapid home HIV testing. A greater proportion indicated being likely to distribute free oral fluid (OF) tests compared to free finger-stick blood (FSB) tests (91% versus 79%), and almost three-fourths (72%) reported being likely to test with their friends or sex partners in the future. MSM not identifying as homosexual/gay were less willing to distribute OF tests, and those with lower educational attainment were more willing to distribute FSB tests. MSM unaware of their HIV status were less likely to report potentially testing with others using free rapid home HIV tests compared to those who were HIV-negative. Finally, MSM willing to self-test were more likely to report future test kit distribution, and those willing to distribute kits were more likely to report potentially testing with others. Engaging individuals with positive attitudes towards these strategies in prevention efforts could help increase HIV testing levels among MSM. A greater understanding of the potential public health impact of rapid home HIV test kits is necessary.

The HIV/AIDS epidemic in the United States continues despite several recent noteworthy advances in HIV prevention. Contemporary approaches to HIV prevention involve implementing combinations of biomedical, behavioral, and structural interventions in novel ways to achieve high levels of impact on the epidemic. Methods are needed to develop optimal combinations of approaches for improving efficiency, effectiveness, and scalability. This article argues that operational research offers promise as a valuable tool for addressing these issues. We define operational research relative to domestic HIV prevention, identify and illustrate how operational research can improve HIV prevention, and pose a series of questions to guide future operational research. Operational research can help achieve national HIV prevention goals of reducing new infections, improving access to care and optimization of health outcomes of people living with HIV, and reducing HIV-related health disparities.

Accurate, reliable and standardized quantification of anti-protective antigen (PA) IgG antibody levels is essential for comparative analyses of anti-toxin immune responses in anthrax cases, recipients of PA-based anthrax vaccines and for evaluation of anti-PA based immunotherapies. We have previously reported the early performance characteristics and application of a quantitative anti-PA IgG enzyme linked immunosorbent assay. The principal application of this assay was in a Phase 4 human clinical trial of anthrax vaccine adsorbed (AVA, BioThrax), the central component of the CDC Anthrax Vaccine Research Program (AVRP) and in humans following bioterrorism associated Bacillus anthracis infection (Quinn et al., 2002; Quinn et al., 2004; Marano et al., 2008). The objective of the AVRP was to determine the feasibility of reducing the number of priming series and booster doses of the licensed Anthrax Vaccine Adsorbed (AVA) (BioThrax®; Emergent BioSolutions, Lansing, MI) and changing the route of administration from subcutaneous (SC) to intramuscular (IM) (Marano et al., 2008). In this paper we report the validation and long term performance characteristics of the assay during its six year application in the AVRP (2002-2008). The critical features are 1) extensive validation of the assay using two standard reference sera; 2) long term stability and 3) consistency of the data for quantitative analysis of human long term anti-PA IgG responses. The reportable value (RV) of the assay was expressed as anti-PA IgG concentration (μg/ml). Accuracy of the assay was high with a percent error (%ER) range of 1.6-11.4%. Overall intra-operator and intermediate precision were high with Coefficients of Variation (%CVs) of 2.5-15.4% and 6.3-13.2%, respectively. The assay demonstrated excellent dilutional linearity for human sera using log(10) transformed data with the slope=0.95 to 0.99, intercept=0.02 to 0.06 and r(2)=0.980-0.987. The assay was robust, tolerating changes in serum incubation temperatures from 35 to 39°C, serum incubation times from 55 to 65min and changes in key reagents. The long-term assay stability over 6years using consecutive reference sera AVR414 and AVR801 demonstrated sustained high accuracy and precision for the assay, confirming its suitability for long term studies of PA protein-based anthrax vaccines., (Published by Elsevier B.V.)

Objective: We determine the feasibility and yield of universal opt-out HIV screening among adolescents and adults in a southeastern emergency department (ED) serving a semiurban-semirural population., Methods: Individuals aged 13 to 64 years who visited the ED during specified hours received the OraQuick rapid HIV test (administered by trained counselors) if they did not opt out. Western blot was used to confirm reactive results. Patients were excluded if they had a history of HIV, had been tested within the past year, were physically or mentally incapacitated, did not understand their right to opt out, or did not speak English or Spanish. Basic demographic information was analyzed by using standard descriptive statistics. Measures of diagnostic test performance were calculated for all valid tests., Results: From March 2008 through August 2009, 91% (n=8,493) of eligible patients accepted testing, and results were valid. Of 41 reactive results, 35 were confirmed HIV positive, 2 were indeterminate by Western blot, and 4 were false positive. Blacks accounted for the largest percentage (0.65%) of newly detected infections, and the percentage among black men (1%) was more than twice the percentage among black women (0.42%). Rapid-test specificity was estimated at 99.95% (95% confidence interval 99.88% to 99.98%). Nearly 75% of patients confirmed as HIV positive kept their first HIV clinic appointment., Conclusion: High rates of acceptance of testing in an ED and linkage to HIV care for adolescents and adults with newly detected infection can be achieved by using opt-out testing and trained HIV counselors., (Copyright © 2011. Published by Mosby, Inc.)

Objectives: The objective was to assess the acceptance of an emergency department (ED) human immunodeficiency virus (HIV) screening program based on the Centers for Disease Control and Prevention (CDC) recommendations for routine HIV screening in health care settings., Methods: Rapid HIV screening was offered on an opt-out basis to patients aged 13 to 64 years presenting to the ED by trained HIV counselors. Patients were excluded if they had a history of HIV, were physically or mentally incapacitated, did not understand their right to opt-out, or did not speak English or Spanish. Statistical analyses, including logistic regression, were performed to assess the associations between the demographics of patients offered testing and their test acceptance or refusal., Results: From March 2008 to January 2009, a total of 5,080 (91%) of the 5,585 patients offered the HIV test accepted, and 506 (9%) refused. White and married patients were less likely to accept testing than those who were African American and unmarried (p < 0.001). Adult patients were almost twice as likely to accept testing as pediatric patients (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.50 to 2.53). As age increased among pediatric patients, testing refusal decreased (OR = 0.71; 95% CI = 0.59 to 0.85), and as age increased among adult patients, testing refusal increased (OR = 1.17; 95% CI = 1.12 to 1.22). Two percent of persons accepting the test were considered high risk. Males were more likely to report high-risk behavior than females (OR = 1.83; 95% CI = 1.23 to 2.72)., Conclusions: The opt-out approach results in high acceptance of routine HIV screening. Widespread adoption of the CDC's recommendations, although feasible, will require significant increases in resources., ((c) 2009 by the Society for Academic Emergency Medicine.)

Quantification of anthrax lethal toxin (LTx) neutralization activity (TNA) is pivotal in assessing protective antibody responses to anthrax vaccines and for evaluation of immunotherapies for anthrax. We have adapted and redesigned the TNA assay to establish a unifying, standardized, quantitative and validated technology platform for LTx neutralization in the J774A.1 murine cell line. Critical design features of this platform are 1) the application of a free-form or constrained 4 parameter logistic (4-PL) function to model neutralization responses within and between boundary limits of 100% cell survival and 95% cell lysis and 2) to exploit innovative assay curve recognition algorithms for interpretive endpoints. The assay was validated using human serum ED50 (dilution of serum effecting 50% neutralization) as the primary reportable value (RV). Intra-operator and intermediate precision, expressed as the coefficient of variation (%CV), were high at 10.5-15.5%CV and 13.5-14.5%CV respectively. TNA assay dilutional linearity was demonstrated for human sera using linear regression analysis of log(10) transformed data with slope=0.99, intercept=-0.03 and r(2)=0.985. Assay accuracy, inferred from the precision and linearity data and using a spike-recovery approach, was high with a percent error (%E) range of only 3.4-20.5%E. The lower limit of detection (LLOD) was ED50=12 and the lower limit of quantification (LLOQ) was ED50=36. The cell-based assay was robust, tolerating incubation temperatures from 35 to 39 degrees C, CO(2) concentrations from 3% to 7% and reporter substrate (MTT) concentrations of 2.5-7.5 mg/ml. Strict assay quality control parameters were met for up to 25 cell culture passages. The long term (50 month) assay stability, determined using human reference standards AVR414 and AVR801, indicated high precision, consistent accuracy and no detectable assay drift. A customized software program provided two additional assay metrics, Quantification Titer (QT) and Threshold Titer (TT), both of which demonstrate acceptable accuracy, precision and dilutional linearity. The TT was also used to establish the assay reactivity threshold (RT). The application of the assay to sera from humans, Rhesus macaques and rabbits was demonstrated separately and by aggregate dilutional linearity analysis of the ED50 (slope=0.98, intercept=0.003, r(2)=0.989). We propose this TNA assay format with a qualified standard reference serum and customized interpretive software as a unifying platform technology for determination of functional serologic responses to anthrax vaccines and for evaluation of anthrax immunotherapeutics.

Interest in changing the milk fatty acid profile is growing. However, little is known about the genetic variability of milk fatty acids in the US Holstein population. Therefore, genetic parameters for milk fatty acids were estimated using a single-trait, mixed, linear animal model on 592 individual milk samples from 233 daughters of 53 sires in a cow herd genetically representative of the US Holstein population. Heritability (h(2)) and repeatability (r) estimates +/- standard errors for yields of individual fatty acids ranged from 0.00 +/- 0.08 (C4:0) to 0.43 +/- 0.13 (C12:0) for heritabilities and from 0.21 +/- 0.05 (C18:1) to 0.43 +/- 0.05 (C12:0) for repeatabilities. Saturated (h(2) = 0.23 +/- 0.12; r = 0.36 +/- 0.05) and de novo synthesized fatty acids (C6:0 to C14:0; h(2) = 0.30 +/- 0.13; r = 0.40 +/- 0.05) had numerically higher estimates than did monounsaturated (h(2) = 0.09 +/- 0.09; r = 0.22 +/- 0.05) and polyunsaturated fatty acids (h(2) = 0.08 +/- 0.09; r = 0.27 +/- 0.05). For relative proportions of individual fatty acids, the greatest heritability and repeatability estimates were obtained for C8:0 (h(2) = 0.18 +/- 0.12; r = 0.36 +/- 0.05), C10:0 (h(2) = 0.22 +/- 0.13; r = 0.46 +/- 0.05), C12:0 (h(2) = 0.18 +/- 0.12; r = 0.46 +/- 0.05), C16:0 (h(2) = 0.09 +/- 0.12; r = 0.48 +/- 0.05), C16:1 (h(2) = 0.49 +/- 0.13; r = 0.49 +/- 0.05), and C18:0 (h(2) = 0.24 +/- 0.11; r = 0.39 +/- 0.05). Our results suggest the existence of genetic variability of milk fatty acids, in particular of medium-and long-chain fatty acids (C8:0 to C18:0), which could be used to improve the nutritional and textural properties of milk fat by selective breeding.

Changing the composition of milk protein and of milk fatty acids alters nutritional and physical properties of dairy products and their consumer appeal. Genetic selection for milk yield decreases concentrations of milk protein and of milk fat. Little is known, however, about how the decrease affects composition of milk protein and milk fatty acids. The objective of this study was to quantify changes in composition of milk protein and of milk fatty acids in cows differing in genetic merit for milk production. Three measures of genetic merit for milk production were used for each cow: genetic line, parent average predicted transmitting ability (PTA) for milk, and cow milk PTA. Composition of milk protein and milk fatty acids were compared in 448 milk samples from 178 cows representing 2 divergent lines of Holsteins that were bred for high or average PTA for milk and combined milk protein and fat yield. High-line cows (n = 97) produced more milk that contained less fat and had higher proportions of alphaS1-casein in milk protein than did average-line cows (n = 81). We additionally obtained from 233 cows (178 cows representing the 2 genetic lines and 55 cows with ancestors from both genetic lines) the parent average milk PTA and cow milk PTA and compared composition of milk protein and of milk fatty acids in 592 milk samples. Cows whose parent average milk PTA was above or equal to the median of the 233 cows produced more milk that contained less protein and less fat and that tended to have greater proportions of alphaS1-casein in milk protein than cows whose average milk PTA was below the median. Similarly, cows with above or equal median milk PTA of the 233 cows produced more milk that contained less protein and less fat and had greater proportions of alphaS1-casein in milk protein than did cows with below-median milk PTA. Milk fatty acid composition was not consistently different between groups. Therefore, selection for milk yield decreased concentrations of milk protein and milk fat but had little effect on composition of milk protein and milk fatty acids.

Changing the milk fatty acid composition can improve the nutritional and physical properties of dairy products and their acceptability to consumers. A more healthful milk fatty acid composition can be achieved by altering the cow's diet, for example, by feeding supplemental fish oil (FO) or roasted soybeans (RSB), or by selecting cows with a more unsaturated milk fatty acid composition. We examined whether feeding supplemental FO or RSB to cows that had a more unsaturated milk fatty acid composition acted additively to produce butter with improved fatty acid composition and texture. Using a 3 x 3 Latin square design with 2 replications, we fed diets to multiparous Holstein cows (60 to 200 DIM) chosen for producing either more or less unsaturated milk fatty acid composition (n = 6 for each group) for three 3-wk periods. The control diet contained 3.7% crude fat and the 2 experimental diets contained, on a dry matter basis, 0.8% of additional lipids in the form of 0.9% of FO or 5% of RSB. The milk, collected in the third week of feeding, was used to make butter, which was analyzed for its fatty acid composition and physical properties. Dry matter intake, milk yield, and milk composition were not significantly affected by cow diet or by cow selection. Cows that produced a more unsaturated and healthful milk fat prior to the feeding study, according to a "health-promoting index" [HPI = (sum of % of unsaturated fatty acids)/ (%12:0 + 4 x %14:0 + %16:0)], maintained a higher HPI in their butter during the feeding study than did cows with a low HPI. Milk from cows fed supplemental FO or RSB yielded more unsaturated butters with a higher HPI. This butter also was softer when the cows were fed RSB. Feeding RSB to cows chosen for their high milk HPI yielded the most unsaturated butter with the highest HPI and softest texture. Thus, selecting cows with a more health-promoting milk fatty acid composition and feeding supplemental RSB can be used in combination to produce butter that has a consumer-friendly texture and a healthful fatty acid profile.

Health data collected from 1996 to 1999 from 177 herds in Minnesota and Wisconsin were analyzed to establish genetic basis for infectious and noninfectious diseases. Three types of health traits were targeted. First, available infectious conditions were used to identify animals that are superior in their general immunity (including innate immunity) for infectious diseases. Generalized immunity may be thought of as a combination of immune responses to a variety of immune system challenges. Second, single infectious and noninfectious diseases were analyzed separately. Third, infectious reproductive diseases as one category of related conditions, and cystic ovary disease as one category of 3 related noninfectious ovary disorders were studied. Data were analyzed using a threshold model that included herd, calving year, season of calving, and parity as cross-classified fixed factors; and sire and cow within sires as random effects. Days at risk and days in milk at the beginning of a record were included by fitting the days as continuous covariates in the model. A heritability value of 0.202 +/- 0.083 was estimated for generalized immunity. Heritability values of 0.141 and 0.161 were estimated for uterine infection and mastitis, respectively. Heritability of single noninfectious disorders ranged from 0.087 to 0.349. The amount of additive genetic variance recovered in the underlying scale of noninfectious disorders tended to zero when combining multiple conditions. The study supports combining infectious diseases into categories of interest but we do not recommend the same approach for noninfectious disorders.

The objective of this study was to determine whether bovine mononuclear leukocytes exhibit genetic variability prior to and after a glucocorticoid hormone challenge in vivo. Test animals included 60 pedigreed Holstein bulls treated on 3 consecutive days with dexamethasone and 5 untreated control bulls. Eight indicator traits of leukocyte responsiveness to dexamethasone included the percentages of circulating B cells, T cells (CD4, CD8, and workshop cluster 1 molecule expressed by bovine gammadelta T cell), major histocompatibility complex (MHC) I and II expressing cells, and mean expressions of surface MHC I and MHC II on circulating cells. Blood for this work was collected from each test bull 10 times before, during, and after dexamethasone administration, with corresponding samples taken for control bulls. Random regression models with treatment-specific serial correlation were applied to the leukocyte data sets to estimate genetic and nongenetic sources of variation in baseline and recovery aspects of the traits. All traits responded predictably to glucocorticoid challenge. Genetic variation was observed in baseline measurements of all traits, with heritability estimates ranging from 0.21 +/- 0.03 to 0.60 +/- 0.06. Genetic variation in linear recovery from nadir values following dexamethasone administration was significant only for percentage CD4, percentage CD8, and for surface expression of MHC II. The genetic covariance between basal and linear recovery was positive and significant for percentage CD4, percentage CD8, and MHC II expression. The bovine lymphocyte antigen DRB3.2 locus accounted for significant proportions of total variation in percentage MHC II cells and MHC I expression. These results suggest that genetic variability exists for important basal and glucocorticoid-modified phenotypes of bovine mononuclear leukocytes, implying that immunocompetence traits impacted by this stress hormone may be enhanced by genetic selection.

Anti-protective antigen (PA) immunoglobulin (Ig) G, toxin neutralization, and PA-specific IgG memory B cell responses were studied in patients with bioterrorism-related cutaneous or inhalation anthrax and in a patient with laboratory-acquired cutaneous anthrax. Responses were determined for >1 year after the onset of symptoms. Eleven days after the onset of symptoms (15 days after likely exposure), anti-PA IgG was detected in 16 of 17 patients with confirmed or suspected clinical anthrax who were tested. Anti-PA IgG remained detectable 8-16 months after the onset of symptoms in all 6 survivors of inhalation anthrax and in 7 of 11 survivors of cutaneous anthrax who were tested. Anti-PA IgG levels and serum toxin neutralizing activity were strongly associated (R2=0.83). PA-specific IgG memory B cells were detectable in all 6 survivors of inhalation anthrax but in only 2 of 7 patients with cutaneous anthrax who were tested. Anti-PA IgG is an important diagnostic marker of anthrax, a predictor of serum anti-toxin activity, and a marker of immunological memory against anthrax.

The objectives of this study were to estimate genetic correlations among body condition scores (BCS) from various sources, dairy form, and measures of cow health. Body condition score and dairy form evaluated during routine type appraisal was obtained from the Holstein Association USA, Inc. A second set of BCS was obtained from Dairy Records Managements Systems (DRMS) and was recorded by producers that use PCDART dairy management software. Disease observations were obtained from recorded veterinarian treatments in several dairy herds in the United States. Estimated breeding values for diseases in Denmark were also obtained. Genetic correlations among BCS, dairy form, and cow health traits in the United States were generated with sire models. Models included fixed effects for age, DIM, and contemporary group. Random effects included sire, permanent environment, herd-year season for health traits, and error. Predicted transmitting abilities (PTA) for BCS and dairy form were correlated with estimated breeding values for disease in Denmark. The genetic correlation estimate between BCS from DRMS and BCS from the Holstein Association USA, Inc., was 0.85. The genetic correlation estimate between BCS and a composite of all diseases in the United States was -0.79, and PTA for BCS was favorably correlated with an index of resistance to disease other than mastitis in Denmark (0.27). Dairy form was positively correlated with a composite of all diseases in the United States (0.85) and was unfavorably correlated with an index for resistance to disease other than mastitis in Denmark (-0.29). Adjustment for protein yield PTA had a minimal affect on correlations between PTA for BCS or dairy form and disease in Denmark. Selection for higher body condition or lower dairy form with continued selection for yield may slow deterioration in cow health as a correlated response to selection for increased yield.

Dairy products from milk of cows fed diets rich in polyunsaturated fatty acids have a more health-promoting fatty acid composition and are softer but often have oxidized flavors. Dairy products made from cow's milk that has more- or less-unsaturated fatty acid compositions were tested for differences in texture and flavor from those made from bulk-tank milk. The milk was manufactured into butter, vanilla ice cream, yogurt, Provolone cheese, and Cheddar cheese. The products were analyzed for fatty acid composition, physical properties, and flavor. Milk of cows with a more monounsaturated fatty acid composition yielded products with a more monounsaturated fatty acid composition that were softer and had a satisfactory flavor. Thus, selection of cows for milk fatty acid composition can be used to produce dairy products that are probably more healthful and have a softer texture.

Recently, the Centers for Disease Control and Prevention reported an accurate, sensitive, specific, reproducible, and quantitative enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum (C. P. Quinn, V. A. Semenova, C. M. Elie et al., Emerg. Infect. Dis. 8:1103-1110, 2002). The ELISA had a minimum detectable concentration (MDC) of 0.06 microgram/ml, which, when dilution adjusted, yielded a whole-serum MDC of 3.0 micro g of anti-PA IgG per ml. The reliable detection limit (RDL) was 0.09 microgram/ml, while the dynamic range was 0.06 to 1.7 microgram/ml. The diagnostic sensitivity of the assay was 97.6% and the diagnostic specificity was 94.2% for clinically verified cases of anthrax. A competitive inhibition anti-PA IgG ELISA was also developed to enhance the diagnostic specificity to 100%. We report a newly developed fluorescence covalent microbead immunosorbent assay (FCMIA) for B. anthracis PA which was Luminex xMap technology. The FCMIA MDC was 0.006 microgram of anti-PA IgG per ml, the RDL was 0.016 microgram/ml, and the whole-serum equivalent MDC was 1.5 micrograms/ml. The dynamic range was 0.006 to 6.8 microgram/ml. Using this system, we analyzed 20 serum samples for anti-PA IgG and compared our results to those measured by ELISA in a double-masked analysis. The two methods had a high positive correlation (r2 = 0.852; P < 0.001). The FCMIA appears to have benefits over the ELISA for the measurement of anti-PA IgG, including greater sensitivity and speed, enhanced dynamic range and reagent stability, the use of smaller sample volumes, and the ability to be multiplexed (measurement of more than one analyte simultaneously), as evidenced by the multiplexed measurement in the present report of anti-PA and anti-lethal factor IgG in serum from a confirmed clinical anthrax infection.

Milk fatty acid composition and textural properties of butter are known to be affected by the cows' diets. We examined the phenotypic variation in milk fatty acid composition among cows fed the same diet to see if the variation was sufficient to produce butter with different textural properties. Ten cows were selected that tested higher (n = 5) or lower (n = 5) in their proportion of milk unsaturated fatty acids. Milk samples were collected a week after testing, and butter was prepared from the individual samples. Milk and butter samples were again analyzed for fatty acid composition. Butter at 5 degrees C was evaluated by a sensory panel for spreadability and by a texture analyzer at both 5 and 23 degrees C for hardness and adhesiveness. Milk and butter samples from cows with a more unsaturated milk fatty acid composition had a lower atherogenic index, and the butter samples were more spreadable, softer, and less adhesive. Thus, phenotypic variation in milk fatty acid composition among cows fed the same diet is sufficient to produce butter with different textural properties.

The advantage of using the genotype of a quantitative trait locus (QTL) in selection schemes of dairy cattle was quantified using stochastic simulation. Three selection plans were studied. In the first plan, young bulls waited for 3 yr until their sisters completed a lactation and then were evaluated and selected based on an animal model. In a second plan, young bulls waited for 5 yr until their daughters completed a lactation. An intermediate 4-yr waiting plan was also studied. Simulation was for 16 yr with overlapping generations. Population and model parameters were proportional to the U.S. Holstein population. The advantage of using a QTL was quantified as the percentage of superiority of QTL-assisted over QTL-free selection using cumulative genetic response. Percentage of superiority was reported for four selection pathways: active sires, young bulls, bull dams, and first lactation cows. A general trend was observed: low superiority in early years of selection that increased to a plateau in later years and then decreased. The superiority of the QTL information was greatest in the 3-yr waiting plan and least in the 4-yr waiting plan. Superiority at plateau for selection pathways ranged from 16 to 26% for the 3-yr waiting plan, from 3 to 12% for the 4-yr waiting plan, and from 5 to 13% for the 5-yr waiting plan. The contribution to selection response attributed to the QTL and the polygenes was quantified. The rate at which the favorable allele approached fixation and the accuracy of predicting breeding values on the percentage of superiority were studied.

The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 micro g/mL, a reliable lower limit of detection of 0.09 micro g/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 micro g/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 97.6%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.

The superiority of selection schemes employing information about a known quantitative trait locus (QTL) over conventional schemes is examined for dairy cattle breeding schemes. Stochastic simulation of a dairy cattle population with selection practices, structures, and parameters similar to the US Holstein population was implemented. Additive genetic effects were estimated by an animal model. Two schemes were compared: a QTL-assisted selection scheme in which the genotype of a known QTL was accounted for in the animal model as a fixed factor, and a QTL-free selection scheme in which the QTL was simulated but was not fit separately in the animal model. Under the QTL-assisted selection scheme, all animals in the mixed model were assumed to be genotyped for the QTL. The effect of using QTL information on the genetic response, the frequency of the favorable QTL allele, and the accuracy of evaluation were examined. Moreover, the effect was studied in four distinct paths of selection: active sires, proven young bulls, bull dams, and first-lactation cows. Average superiority values of 4.6, 7.6, 11.7, and 1.1% for genetic response were observed over 16 yr of selection for active sires, young bulls, bull dams, and first-lactation cows, respectively. Frequency of the favorable QTL allele changed faster in bull dams than males, and was the slowest in first-lactation cows. Finally, accuracy of evaluation under the QTL-assisted selection scheme was higher than under the QTL-free selection scheme. Young bulls ofthe QTL-assisted selection scheme on average had 0.049 higher accuracy, and first-lactation cows had on average 0.185 higher accuracy than corresponding animals of the QTL-free selection scheme.

Teat-end shapes were categorized for 1443 Holstein cows with 3582 lactations, in the Iowa State University herd at Ankeny, approximately 40 d postpartum between 1970 and 1995. Frequencies of teat-end shapes were as follows: round, 52.2%; prolapsed, 0.8%; flat, 14.2%; plate, 3.4%; funnel, 8.9%; and mixed, 20.5%. Cows were coded as mixed if all four teat-end shapes were not the same. Heritability estimates were obtained with an animal model with pedigrees traced back to registration numbers roughly conforming to birth year 1955. The heritability estimates for first, second, and third and later lactations were 34, 21, and 13%, respectively. Lactation averages for linear somatic cell scores were adjusted for days in milk, and month and age at calving, and were available for 255 cows with 431 lactations categorized from 1992 to 1995. Frequencies of teat-end shape on the 255 cows were as follows: round, 58%; prolapsed, 3%; flat, 11%; plate, 2%; funnel, 6%; and mixed, 20%. Least-squares means of somatic cell score for categories of teat-end shape were computed from a mixed model that included year, parity, and teat-end shape as fixed effects and cow as a random effect. Teat-end shape did not significantly affect somatic cell score.

A great deal of evidence points to substantial genetic control over at least some of the immune responses, although genetic parameters for clinical disease have been less favorable. The past two decades have illustrated that single genes with a large impact on food animal health do exist and can be used to improve the health of domestic populations. The current focus on molecular genetics within food animal species will likely unveil numerous other examples of single genes with large effects, although the use of animals possessing favorable genotypes for disease resistance may represent a compromise in selection for increased production of raw product. Moreover, it is also clear that genetic control over the immune system is not limited to a few genes but is more likely influenced by many genes, each with small effects. The use of this information in animal improvement programs is not straightforward because of factors complicating the identification of superior individuals within the population. The scarcity of information dealing with phenotypic and genetic relationships between measures of disease resistance and aspects of immune response complicates the situation even further. Despite these potential hurdles, the potential for permanent improvement of disease resistance within food animal species in the future is tantalizing and merits intensified future study.

The inverse of the gametic covariance matrix between relatives, G(-1), for a marked quantitative trait locus (QTL) is required in best linear unbiased prediction (BLUP) of breeding values if marker data are available on a QTL. A rapid method for computing the inverse of a gametic relationship matrix for a marked QTL without building G itself is presented. The algorithm is particularly useful due to the approach taken in computing inbreeding coefficients by having to compute only few elements of G. Numerical techniques for determining, storing, and computing the required elements of G and the nonzero elements of the inverse are discussed. We show that the subset of G required for computing the inbreeding coefficients and hence the inverse is a tiny proportion of the whole matrix and can be easily stored in computer memory using sparse matrix storage techniques. We also introduce an algorithm to determine the maximum set of nonzero elements that can be found in G(-1) and a strategy to efficiently store and access them. Finally, we demonstrate that the inverse can be efficiently built using the present techniques for very large and inbred populations.

Measurement of direct and correlated responses to single-trait selection for milk yield was the major objective of regional project NC-2. The NC-2 Technical Committee included representatives from Alaska, Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Nebraska, South Dakota, Wisconsin, and the USDA. All representatives, except Illinois, Kansas and Nebraska, maintained a selection line formed by using AI sires selected for high estimated transmitting abilities for milk and a second line that served as some type of a control. Stations varied in criteria for selection of bulls for control lines. Farms were managed similarly, including feeding and management of selection and control lines as one herd, random mating within line, and restricted culling policies. Selection for milk yield effectively increased milk production. All selection lines increased milk and net income per lactation more than control lines. Realized gains matched or exceeded gains expected from estimates of breeding values. Yields of milk components increased, but component percentages decreased appreciably for selection lines. Reproduction of nulliparous animals was not affected, but days open for lactating selection cows increased in some of the individual projects. Selected cows tended to have larger health costs, specifically for mammary treatment. Udder and conformation traits did not deteriorate for selection lines, although control lines with selection of sires on genetic evaluations for type received higher type scores. There should be few reservations about undesirable responses correlated with selection for milk yield.

A mitochondrial DNA (mtDNA) fragment containing the D-loop, phenylalanine tRNA, valine tRNA, and 12S and 16 rRNA genes was cloned and sequenced from 36 cows of 18 maternal lineages to identify the polymorphic sites within those regions and to detect the existence of heteroplasmic mtDNA in cows. Seventeen variable sites were observed within the D-loop and rRNA coding regions of bovine mtDNA within a 2.5-kb span. The hypervariable sites in the D-loop and rRNA coding regions were identified at nucleotide positions 169, 216, and 1594. Heteroplasmic mtDNA (variable mtDNA within a tissue) existed extensively in cows and was detected within the above regions in 11 of 36 cows sequenced. The insertion, deletion, and nucleotide transversion polymorphisms were found only in homopolymer regions. Heteroplasmy was observed frequently and seemingly is persistent in cattle. Though heteroplasmy was demonstrated, most lineages and mtDNA sites showed no heteroplasmy.

The effects of kappa-casein (CN) and beta-lactoglobulin (LG) genotypes on milk protein concentration and composition were estimated for the US Holstein-Friesian population using a single-trait, mixed, linear animal model on 592 individual milk samples from 233 cows. Both milk protein genotypes had no statistically significant effect on the total milk protein concentration; however, substitution of the kappa-CN A allele additively increased the proportion of kappa-CN, and substitution of the beta-LG B allele additively increased the proportion of beta-LG in total milk protein. In response, proportions of the other milk proteins, mainly alpha S1-CN, were decreased. For proportions of alpha S1-CN, kappa-CN, and beta-LG in total milk protein, kappa-CN and beta-LG genotypes explain more than 50 and 25% of the heritability and repeatability estimates, respectively. We concluded that kappa-CN and beta-LG genotypes affect the phenotypic and genetic variation of milk protein composition but do not significantly affect milk protein concentration. A possible explanation for our conclusion is that altered gene sequences in the promoter region of kappa-CN B and beta-LG A, linked closely to the respective genotypes, favor the transcription or translation of their own protein at the expense of the synthesis of other milk proteins, in particular of alpha S1-CN.

Associations among quantities and concentrations of individual milk proteins and fatty acids were determined in individual milk samples from 233 Holstein cows. Correlation coefficients among the six major proteins and the eleven major fatty acids in bovine milk were grouped hierarchically. Factor analyses grouped the milk components into seven families: fatty acids 4:0-6:0, 6:0-16:0, 16:0, 18:0, 16:1 plus 18:1 plus 18:2, all milk proteins and beta-lactoglobulin alone. Correlation coefficients and groupings by factor analyses coincided with shared pathways of synthesis or genetic origins of milk proteins and fatty acids because they are the basis of the correlation coefficients. Hence, the results from correlations and factor analyses could be used to develop hypotheses for the synthesis of milk components and other coordinately regulated physiological processes.

A pedigree analysis was used to investigate the association of bovine growth hormone loci with milk production traits of Holstein cattle. Holstein bulls were typed for three bovine growth hormone loci located in exon V, intron C, and the 3' region of the gene. Phenotypic data were daughter yield deviations for milk, fat, and protein yields and for fat and protein percentages. Analysis of linkage across families was applied to the data using one or two bovine growth hormone loci as markers linked to a putative biallelic quantitative trait locus. Estimated parameters were allele frequency, genotypic means, within-genotype standard deviation of a putative quantitative trait locus, and recombination fraction between the markers and the quantitative trait locus. Parameters were estimated by maximum likelihood techniques. The estimated frequency of the quantitative trait locus allele that decreased the value of the phenotype ranged from 0.1 for milk yield to 0.6 for protein yield. The estimated effect of an allele substitution at the quantitative trait locus, given in phenotypic standard deviation units, ranged from 0.75 for fat percentage to 1.6 for milk yield. The standard deviation within genotype ranged from 0.67 for fat yield to 0.87 for milk yield. The estimated recombination fraction was close to zero for protein percentage, indicating physical linkage between a quantitative trait locus affecting the trait and the bovine growth hormone loci.

Phagocytosis and oxidative burst activity of polymorphonuclear neutrophil leukocytes (PMN) isolated from blood and pregnancy-associated glycoprotein (bPAG) concentrations in plasma were evaluated in two longitudinal studies in dairy cows from 3 weeks before until 5 weeks after calving, carried out in the United States and in Europe. Ingestion of Staphylococcus aureus by blood PMN increased during the first week after calving and normalised 3 weeks post-partum. Phagocytosis of Escherichia coli did not change in the early post-partum period. In both studies, a significant decrease in oxidative burst activity of PMN was observed between 1 and 3 weeks after calving. In all cows, a very significant increase in plasma bPAG concentration was found between 1 week before and 2 weeks after calving. The peak of bPAG concentration in plasma immediately preceded the alterations of blood PMN functions. These results suggest that bPAG may be associated with inhibition of PMN function of dairy cows during the early post-partum period.

Current analytical methods for milk proteins lack the capacity to simultaneously separate and quantify the six major bovine milk proteins and their genetic variants. A method is described that simultaneously separates and quantifies the six major bovine milk proteins. The separation is based on reversed-phase partitioning of the six major milk proteins and several genetic variants of kappa-casein, beta-casein, and beta-lactoglobulin. The described method has for each of the six milk proteins a linear quantitative response, precision (coefficient of variation below 5.1% within days of analysis, and below 7.1% between days of analysis), resolution (over 2.5 between proteins), peak efficiency (theoretical plate numbers between 8 000 and 50 000), and a sample treatment without filtration steps that together with the analysis takes 2 h. The composition of protein from milk of each of 234 cows was determined using the current method, and the results were similar to reference values for milk proteins.

Relationships between genetic measures of mastitis (somatic cell score, score for clinical mastitis, and scores for IMI with major or minor pathogens) and immunological parameters (physiological and molecular markers) were examined for periparturient Holstein cows. Physiological markers included 11 in vitro immunological assays. Molecular markers included the second exon of the DRB3 locus of the bovine major histocompatibility complex, the IgG2 isotype genotype, and the CD18 genotype (the locus responsible for bovine leukocyte adhesion deficiency). A gene substitution model was used to estimate the additive genetic effects of alleles of the three molecular markers on estimated breeding value (EBV) for mastitis measures. Pearson correlation coefficients between EBV for immunological assays and EBV for mastitis measures were computed. Molecular markers explained up to 40% of the variation in EBV for measures of mastitis. The presence of allele DRB3.2*16 was associated with higher EBV for SCS. Allele DRB3.2*8 was associated with increased EBV for clinical mastitis, as was the IgG2b allele and the normal CD18 allele. Alleles DRB3.2*11, *23, IgG2a, and the recessive allele for bovine leukocyte adhesion deficiency were associated with decreased clinical mastitis. A positive genetic association was found between allele DRB3.2*24 and EBV for IMI by major pathogens and between DRB3.2*3 and IMI by minor pathogens. Several correlations between EBV for immunological assays and EBV for mastitis measures were significantly different from 0. Cows with low EBV for SCS tended to have neutrophils that had greater functional ability at maximal immunosuppression, low serum IgG1, and high numbers of circulating mononuclear cells. Immunological parameters, including physiological and molecular markers, are useful aids to understand the genetics of resistance to mastitis.

The objective of this study was to determine whether differences in first lactation production, unadjusted or adjusted for days open, were correctly predicted by pedigree estimates for two lines of Holstein cattle. Data on 875 cows from two selection lines were collected from 1970 to 1988. Lines were created by mating foundation females of high or low pedigree merit to sires selected for high or average PTA milk. Both lines were managed identically to minimize environmental differences. The number of days open was analyzed with a fixed effects model containing year, season, interaction of year and season, sire line, foundation group, and interaction of sire line and foundation groups. The high milk line had significantly more days open than did the average line. Adjusted and unadjusted records for milk and fat were analyzed with the model described previously, plus the interaction of sire line and year. Least squares means and estimates for mean parent average were used to calculate realized and expected differences in production between lines within and across years. Adjustment of records for days open reduced estimates of realized gain, but not significantly. Regressions of realized gain on expected gain indicated that expected gains were matched or exceeded by unadjusted or adjusted realized gain.